Prediction of efficacy of early-stage tumor markers combined with NLR and PLR for immunotherapy in gastric cancer / 国际肿瘤学杂志

Objective:To explore the predictive value of early serum tumor markers (STM) , neutrophil to lymphocyte ratio (NLR) , platelet to lymphocyte ratio (PLR) combination score on the efficacy of gastric cancer immunotherapy.Methods:A total of 76 patients with gastric cancer who received immunotherapy at Second Affiliated Hospital of Shandong First Medical University from January 1, 2020 to June 30, 2022 were selected. Patients' leading STM, NLR, PLR were collected. Optimal cut-off value of NLR and PLR were determined by the receiver operating characteristic (ROC) curve. The clinical efficacy and prognosis of different leading STM, NLR, PLR and combined scores in gastric cancer patients received immunotherapy were analyzed. ROC curve was used to evaluate the predictive efficiency of each index and the combined score. Cox regression model was used to analyze the factors affecting patients' survival.Results:The best truncation value for NLR was 2.75, and the best truncation value for PLR was 175.9. All patients completed at least 2 cycles of immunotherapy, the objective response rate (ORR) was 23.7% (18/76) , and the disease control rate (DCR) was 88.2% (67/76) . There were no significant differences in ORR [ (20.9% (9/43) vs. 27.3% (9/33) ], DCR [83.7% (36/43) vs. 93.9% (31/33) ] between the high NLR group ( n=43) and low NLR group ( n=33) ( χ2=0.42, P=0.519; χ2=1.02, P=0.313) . There were no significant differences in ORR [27.3% (12/44) vs. 18.8% (6/32) ], DCR [81.8% (36/44) vs. 96.9% (31/32) ] between the high PLR group ( n=44) and low PLR group ( n=32) ( χ2=0.75, P=0.388; χ2=2.71, P=0.555) . The ORR for the high combined score group ( n=39) and low combined score group ( n=37) was 17.9% (7/39) and 29.7% (11/37) , respectively, with no statistically significant difference ( χ2=1.46, P=0.230) ; the DCR was 79.5% (31/39) and 97.3% (36/37) , respectively, with a statistically significant difference ( χ2=4.19, P=0.041) . The median progression free survival (PFS) and overall survival (OS) of 76 patients were 8.0 and 12.0 months. The median PFS in the high NLR group and low NLR group was 7.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=7.95, P=0.005) ; the median OS was 12.0 and 14.0 months, respectively, with no statistically significant difference ( χ2=1.04, P=0.307) . The median PFS in the high PLR group and low PLR group was 8.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=3.90, P=0.048) ; the median OS was 13.0 and 13.0 months, respectively, with no significant difference ( χ2=0.02, P=0.896) . The median PFS in the high combined score group and low combined score group was 7.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=13.52, P<0.001) ; the median OS was 12.0 and 14.0 months, respectively, with a statistically significant difference ( χ2=5.02, P=0.025) . ROC curve analysis showed that the area under curve (AUC) of leading STM, NLR, PLR and combined score to predict the efficacy of gastric cancer immunotherapy was 0.662, 0.697, 0.601 and 0.773. Univariate analysis showed that, surgery ( HR=0.59, 95% CI: 0.36-0.95, P=0.031) , leading STM ( HR=0.57, 95% CI: 0.34-0.93, P=0.026) , NLR ( HR=0.54, 95% CI: 0.34-0.87, P=0.011) , combined score ( HR=0.42, 95% CI: 0.26-0.68, P<0.001) were all influencing factors for PFS in gastric cancer patients received immunotherapy; tumor stage ( HR=0.30, 95% CI: 0.12-0.75, P=0.011) , leading STM ( HR=0.28, 95% CI: 0.15-0.50, P<0.001) , combined score ( HR=0.55, 95% CI: 0.31-0.96, P=0.036) were all influencing factors for OS in gastric cancer patients received immunotherapy. Multivariate analysis showed that, leading STM ( HR=0.56, 95% CI: 0.33-0.98, P=0.041) was an independent influencing factor for PFS in gastric cancer patients received immunotherapy; tumor stage ( HR=0.29, 95% CI: 0.11-0.76, P=0.012) , leading STM ( HR=0.32, 95% CI: 0.17-0.58, P<0.001) , combined score ( HR=0.46, 95% CI: 0.25-0.82, P=0.009) were all independent influencing factors for OS in gastric cancer patients received immunotherapy. Conclusion:The combined score of leading STM, NLR and PLR is an independent factor influencing OS in patients receiving immunotherapy for gastric cancer, and can predict the efficacy of immunotherapy for gastric cancer.

Advances in predicting efficacy and prognostic markers of immunotherapy for gastric cancer / 国际肿瘤学杂志

The high intra- and inter-tumor heterogeneity of gastric cancer leads to a great difference in the immunotherapy efficacy and the prognosis among patients. Several biomarkers, including programmed death-ligand 1, human epidermal growth factor receptor 2, the features of tumor microenvironment, the peripheral blood inflammatory markers and Claudin18.2 have predictive value in the immunotherapy efficacy and the prognosis of gastric cancer patients, which might help the clinicians find the potential patients who will benefit from immunotherapy, and achieve the goal of precision medicine.

Expert consensus on the molecular diagnosis of early-stage pancreatic cancer （2023 edition） / 临床肝胆病杂志

Pancreatic cancer is a relatively common tumor of the digestive system， with difficulties in early-stage diagnosis and an extremely high degree of malignancy. Molecular diagnostic technology based on tumor biomarkers， combined with the existing gold standard in clinical practice， is of great clinical significance to achieve early accurate identification， timely treatment and intervention， and reduction in mortality. Previous studies have shown that miRNAs show high specificity in terms of types and expression levels in different pathological stages of pancreatic cancer and can thus be used in monitoring the development and progression of pancreatic cancer. Since a single miRNA has a limited diagnostic potential， the combination of different miRNAs may effectively improve the diagnostic efficiency of early-stage pancreas carcinogenesis. Based on related research advances in recent years， this consensus document aims to fill the gap in molecular diagnostic technology in the guidelines for the clinical diagnosis and treatment of pancreatic cancer and provide expert guidance and recommendations.

Clinical efficacy of tirellizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer / 中国基层医药

Objective:To investigate the efficacy of tirellizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer and its effect on immune function and quality of life in patients.Methods:In this retrospective case-control study, we analyzed the clinical data of 104 patients with advanced (stages III and IV) non-small cell lung cancer who received treatment at Zhoushan Hospital between May 2021 and June 2022. These patients were divided into two groups: group A ( n = 52) and group B ( n = 52), based on the treatment methods utilized. Patients in group A received chemotherapy with gemcitabine plus cisplatin or pemetrexed plus cisplatin. Meanwhile, patients in group B were treated with tirellizumab combined with chemotherapy regimens of gemcitabine plus cisplatin or pemetrexed plus cisplatin, with 21 days as a treatment cycle. Both groups of patients received three cycles of treatment. The short-term efficacy was compared between the two groups. Additionally, serum levels of tumor markers, immune function indexes, quality of life score, and incidence of adverse reactions were compared between the two groups before and after treatment. Results:The short-term response rate in group B was significantly higher than that in group A [51.92% (27/52) vs. 32.69% (17/52), Z = 4.11, P < 0.001]. When compared with pretreatment levels, serum levels of tumor markers and the percentage of CD8 + cells decreased in both groups after treatment. Notably, the serum levels of tumor markers and the percentage of CD8 + cells were significantly lower in group B compared with group A (all P < 0.05). Moreover, after treatment, the percentage of CD4 + cells, the ratio of CD4 +/CD8 + cells, functional subscale, symptom subscale, and total score increased significantly compared with pretreatment levels (all P < 0.05) and were significantly higher in group B compared with those in group A (all P < 0.05). The incidence of adverse events in group B was significantly higher than that in group A [44.23% (23/52) vs. 21.15% (11/52), χ2 = 6.29, P = 0.012]. Conclusion:Tirelizumab combined with chemotherapy is effective for advanced non-small-cell lung cancer. The combined therapy can lower serum levels of tumor markers, restore immune function, and improve overall quality of life.

Prognostic value of MET, Cyclin D1, and MET gene copy number for non-small cell lung cancer / 中国基层医药

Objective:To analyze the prognostic value of MET, Cyclin D1, and MET gene copy number (GCN) for non-small cell lung cancer (NSCLC).Methods:This study included 61 patients with NSCLC who received treatment at the Enze Hospital, Taizhou Enze Medical Center (Group) between January 2018 and June 2019. The expression levels of MET and Cyclin D1 were determined using immunohistochemistry. MET GCN was evaluated using a quantitative polymerase chain reaction. Clinicopathological characteristics were compared among patients with different expression levels of these proteins. The Spearman correlation coefficient was used to assess the relationship between MET, Cyclin D1, and MET GCN. The Kaplan-Meier method was used to analyze survival rates. Univariate and multivariate Cox regression analyses were conducted to investigate the correlation between MET, Cyclin D1, and MET GCN and survival rates.Results:Thirty-six cases (59.02%) tested positive for MET, which was mainly expressed in the cytoplasm and membrane. Similarly, 36 cases (59.02%) were positive for Cyclin D1, which was mainly expressed in the cytoplasm. Patients with MET ( χ2 = 6.89, P = 0.009) and MET/Cyclin D1 ( χ2 = 4.05, P = 0.004) had a high proportion of poorly differentiated histology. Moreover, patients with MET GCN ≥ 3 had a relatively high proportion of lymph node metastasis ( χ2 = 8.11, P = 0.004) and TNM stages III-IV ( χ2 = 3.91, P = 0.048). Furthermore, patients with MET GCN ≥ 3/Cyclin D1 also had a high proportion of lymph node metastasis ( χ2 = 6.73, P = 0.009). MET was significantly associated with MET GCN ( r = 0.39, P = 0.002) and Cyclin D1 ( r = 0.39, P = 0.002), while MET GCN was significantly associated with Cyclin D1 ( r = 0.30, P = 0.017). The median survival time of patients with and without MET was 24.0 and 32.5 months, respectively, while the median survival time of patients with MET GCN ≥ 3 and < 3 was 11.0 and 30.5 months, respectively. Multivariate analysis showed that TNM stages III-IV, positive expression of MET, and MET GCN ≥ 3 were significantly associated with a high risk of death. Conclusion:The positive expression of MET and MET GCN ≥ 3 may be adverse prognostic factors in patients with NSCLC. The activation of the MET/Cyclin D1 signaling pathway could potentially contribute to the development and progression of NSCLC.

The value of six tumor markers in preoperative diagnosis and prognostic evaluation of advanced serous ovarian cancer / 中国医师杂志

Objective:To explore the diagnostic and prognostic value of six tumor markers, namely carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), carbohydrate antigen 153 (CA153), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724), in the pathological types of epithelial ovarian cancer (EOC).Methods:A retrospective analysis was conducted on the preoperative tumor markers and clinical pathological data of 131 EOC patients admitted to the First Affiliated Hospital of Shihezi University from January 2010 to May 2022, and follow-up was conducted. Patients were divided into high-grade serous ovarian cancer (HGSOC) group and other groups (mucinous cancer, endometrioid carcinoma, clear cell carcinoma, mixed carcinoma) according to pathological type and tumor grade. We investigated the correlation between the levels of six tumor markers and the pathological types of EOC. By drawing receiver operating characteristic (ROC) curves and comparing the area under the curve (AUC), we also investigated the diagnostic value of single and combined detection of six tumor markers for the pathological types of EOC. K-M survival analysis was used to explore the impact of tumor markers on patient prognosis.Results:The levels of CA125 and CA153 in the HGSOC group were significantly higher than those in other pathological groups ( Z=-2.571, -5.416, all P<0.05); CA153 had good diagnostic performance for HGSOC (AUC=0.777), and the combined detection of CA125+ CA153, CA153+ AFP, CA153+ CA199, CA153+ CA724, CA153+ CE had better diagnostic performance than the single detection of CA125 and CA153 (AUC=0.781, 0.784, 0.809, 0.803, 0.773). Among them, the combined detection of CA125, CA153, and CA199 had the best diagnostic performance (AUC=0.816, Youden′s index 0.532); the elevated levels of CA153 and CA153+ CA199 indicated poor recurrence free survival (PFS) in patients (all P<0.05), while the elevated levels of CA153+ CA199 was an independent risk factor for recurrence in patients ( P=0.022); the elevated levels of CA153+ CA199 and CA125+ CA153+ CA199 indicated poorer OS in patients (all P<0.05). Conclusions:The serum levels of CA125 and CA153 are elevated in patients with HGSOC. Elevated levels of CA153, CA153+ CA199, and CA125+ CA153+ CA199 are associated with poor prognosis in patients. The combined detection of CA125, CA153, and CA199 has the best diagnostic efficacy and can serve as a potential biomarker for assisting in the diagnosis of HGSOC and evaluating patient prognosis.

The diagnostic value of CA125, CEA, CYFRA21-1, CA19-9, and SCC-Ag in lung adenocarcinoma and their predictive value for postoperative recurrence / 中国医师杂志

Objective:To explore the diagnostic value of serum tumor marker detection for lung adenocarcinoma and its predictive value for postoperative recurrence.Methods:A total of 100 lung adenocarcinoma patients (modeling group) and 100 benign lung disease patients (control group) admitted to the Cangzhou Hospital of Integrated Traditional and Western Medicine from December 2018 to December 2020 were selected as the research subjects. In addition, 50 lung adenocarcinoma patients admitted from December 2016 to December 2017 were selected as the validation group. The serum carbohydrate antigen 125 (CA125) and carcinoembryonic antigen (CEA) levels of the modeling group and the control group were compared Levels of cytokeratin 21 fragment (CYFRA21-1), carbohydrate antigen 19-9 (CA19-9), and squamous cell carcinoma antigen (SCC-Ag). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of CA125, CEA, CYFRA21-1, CA19-9, and SCC-Ag alone and in combination for lung adenocarcinoma; Single and multiple factor analyses were conducted to identify the risk factors for postoperative recurrence in lung adenocarcinoma patients; A column chart model for predicting postoperative recurrence in lung adenocarcinoma patients was constructed using R software, and a risk stratification system was constructed.Results:The average water levels of CA125, SCC-Ag, CEA, CYFRA21-1, and CA19-9 in the modeling group were significantly higher than those in the control group (all P<0.05). The ROC curve showed that the combined detection of CA125, CEA, CYFRA21-1, CA19-9, and SCC-Ag had high diagnostic value for lung adenocarcinoma, with an area under the curve (AUC) of 0.903 (95% CI: 0.865-0.954); Elevated levels of CEA, CA125, CA19-9, and CYFRA21-1 were independent risk factors for postoperative recurrence in lung adenocarcinoma patients (all P<0.05). Patients were divided into extremely low-risk group (total score<56 points), low-risk group (56 points≤total score<132 points), medium risk group (132 points≤total score<186 points), and high-risk group (total score≥186 points) through risk stratification. The survival curve results showed that there was a statistically significant difference in postoperative recurrence rate among patients with different risk stratification systems ( P<0.05). Conclusions:The combined detection of CA125, CEA, CYFRA21-1, CA19-9, and SCC-Ag has high diagnostic value for lung adenocarcinoma. Among them, CA125, CEA, CYFRA21-1, and CA19-9 have certain predictive value for postoperative recurrence in patients.

Cáncer de mama en el norte del Perú: subtipos moleculares y HER2 low / Breast cancer in northern Peru: molecular subtypes and HER2 low

RESUMEN El objetivo del estudio fue conocer el perfil inmunohistoquímico del cáncer de mama e identificar el subgrupo HER2 low en la macrorregión norte del Perú. Se realizó un estudio transversal con una muestra de 1176 pacientes atendidos en el Instituto Regional de Enfermedades Neoplásicas Norte del Perú desde enero de 2016 a diciembre de 2023. Los datos recolectados (edad, tipo histológico, grado y resultados complementarios), se analizaron con frecuencias y porcentajes. El perfil correspondió a: luminal B (45,6%); luminal A (24,7%); triple negativo (18,2%); y HER2 positivo no luminal (11,5%). Además, HER2 low fueron 215 pacientes (25,1% de los considerados previamente negativos). Este estudio proporciona evidencia que la subtipificación de cáncer de mama ha cambiado, siendo luminal B más frecuente, y es esencial involucrar a políticas de salud para adquirir terapias dirigidas considerando a pacientes HER2 low.

ABSTRACT This study aimed to understand the immunohistochemical profile of breast cancer and to identify the HER2 low subgroup in the northern macro-region of Peru. A cross-sectional study was conducted in 1176 patients from the Regional Institute of Neoplastic Diseases Northern Peru, from January 2016 to December 2023. We analyzed the data (age, histological type, grade and complementary results), with frequencies and percentages. The profile corresponded to: luminal B (45.6%); luminal A (24.7%); triple negative (18.2%); and HER2 positive non luminal (11.5%). In addition, 215 patients presented HER2 low (25.1% of those previously considered negative). This study provides evidence that the subtyping of breast cancer has changed, being luminal B the most frequent. It is essential to involve health policies to acquire targeted therapies considering HER2 low patients.

Niveles de β2microglobulina, variables clínicas y sociodemográficas en pacientes con síndrome linfoproliferativo crónico de reciente diagnóstico

Fundamento: la β2microglobulina está reconocida como marcador tumoral para diferentes propósitos en hematopatías malignas de estirpe linfoide; sin embargo, no hay antecedentes de su utilización en la provincia de Cienfuegos. Objetivo describir las características sociodemográficas, clínicas y la distribución de los niveles séricos de β2microglobulina en pacientes con síndrome linfoproliferativo crónico y su relación con los estadios clínicos y la respuesta al tratamiento de primera línea. Métodos: estudio observacional descriptivo transversal. La serie se conformó con todos los pacientes adultos con diagnóstico reciente (sin comenzar terapia antitumoral específica) de mieloma múltiple, leucemia linfoide crónica, linfoma no Hodgkin y linfoma Hodgkin, ingresados en el Servicio de Hematología del Hospital General Universitario Dr. Gustavo Aldereguìa Lima, durante el año 2020. La información se obtuvo mediante revisión documental de historias clínicas y ensayos de laboratorio. Se analizaron las variables: sexo, edad, color de la piel, niveles de β2microglobulina, tipo de enfermedad, estadios clínicos y respuesta al tratamiento. Resultados: el 84 % de la serie presentó niveles elevados del analito, más acentuado en el mieloma. Se constató relación entre los niveles estratificados de β2microglobulina con los estadios clínicos y la respuesta al tratamiento de primera línea. Conclusiones: las características sociodemográficas y las variables clínicas observadas no difieren de forma sustantiva con lo reportado. La distribución de los niveles de la β2microglobulina es sugerente de una relación directa entre los estadios clínicos e inversa con la respuesta al tratamiento.

Background: β2microglobulin is recognized as a tumor marker for different purposes in malignant hematopathies of lymphoid lineage; however, there is no history of its use in the Cienfuegos province. Objective: to describe the sociodemographic and clinical characteristics and the distribution of serum β2microglobulin levels in patients with chronic lymphoproliferative syndrome and their relationship with clinical stages and response to first-line treatment. Methods: cross-sectional descriptive observational study. The series was made up of all adult patients (universe 50) recently diagnosed (without starting specific antitumor therapy) of multiple myeloma, chronic lymphoid leukemia, non-Hodgkin lymphoma and Hodgkin lymphoma, admitted to the Hematology Service of the Dr. Gustavo Aldereguìa Lima General University Hospital, during the year 2020. The information was obtained through documentary review of medical records and laboratory tests. The analyzed variables were: sex, age, skin color, β2microglobulin levels, type of disease, clinical stages and response to treatment. Results: 84% of the series presented high levels of the analyte, more accentuated in myeloma. A relationship was found between the stratified levels of β2microglobulin with the clinical stages and the response to first-line treatment. Conclusions: the sociodemographic characteristics and the clinical variables observed do not differ substantially from what was reported. The distribution of β2microglobulin levels is suggestive of a direct relationship between clinical stages and an inverse relationship with response to treatment.

Identification of novel biomarkers with potential for diagnosis and prognosis of gastric cancer: a bioinformatics approach

INTRODUCTION: Gastric cancer (GC) is the fifth most diagnosed neoplasia and the third leading cause of cancer-related deaths. A substantial number of patients exhibit an advanced GC stage once diagnosed. Therefore, the search for biomarkers contributes to the improvement and development of therapies. OBJECTIVE: This study aimed to identify potential GC biomarkers making use of in silico tools. METHODS: Gastric tissue microarray data available in Gene Expression Omnibus and The Cancer Genome Atlas Program was extracted. We applied statistical tests in the search for differentially expressed genes between tumoral and non-tumoral adjacent tissue samples. The selected genes were submitted to an in-house tool for analyses of functional enrichment, survival rate, histological and molecular classifications, and clinical follow-up data. A decision tree analysis was performed to evaluate the predictive power of the potential biomarkers. RESULTS: In total, 39 differentially expressed genes were found, mostly involved in extracellular structure organization, extracellular matrix organization, and angiogenesis. The genes SLC7A8, LY6E, and SIDT2 showed potential as diagnostic biomarkers considering the differential expression results coupled with the high predictive power of the decision tree models. Moreover, GC samples showed lower SLC7A8 and SIDT2 expression, whereas LY6E was higher. SIDT2 demonstrated a potential prognostic role for the diffuse type of GC, given the higher patient survival rate for lower gene expression. CONCLUSION: Our study outlines novel biomarkers for GC that may have a key role in tumor progression. Nevertheless, complementary in vitro analyses are still needed to further support their potential.

Analysis of microsatellite instability in endometrial cancer: The significance of minimal microsatellite shift / 北京大学学报(医学版)

OBJECTIVE@#To analyze the differences and characteristics of microsatellite instability (MSI) in endometrial cancer (EMC), by using colorectal cancer (CRC) as control.@*METHODS@#In the study, 228 cases of EMC were collected. For comparative analysis, 770 cases of CRC were collected. Mismatch repair (MMR) expression was detected by immunohistochemistry (IHC), and microsatellite instability (MSI) was analyzed by PCR and capillary electrophoresis fragment analysis (MSI-PCR). MSI-PCR was detected using five mononucleotide repeat markers: BAT-25, BAT-26, NR-21, NR-24, and MONO-27.@*RESULTS@#In EMC, we found 27.19% (62/228) of deficient mismatch repair (dMMR) using IHC, significantly higher than CRC (7.79%, 60/770). Meanwhile, subclonal expression of MMR protein was found in 4 cases of dMMR-EMC and 2 cases of dMMR-CRC. According to the criteria of major micro-satellite shift, we found 16.23% (37/228) of MSI-high (MSI-H), 2.63% (6/228) of MSI-low (MSI-L), and 81.14% (185/228) of microsatellite stability (MSS) in EMC using MSI-PCR. The discor-dance rate between MMR-IHC and MSI-PCR in EMC was 11.84% (27/228). In CRC, we found 8.05% (62/770) of MSI-H, 0.13% (1/770) of MSI-L, and 91.82% (707/770) of MSS. The discordance rate between MMR-IHC and MSI-PCR in CRC was only 0.52% (4/770). However, according to the criteria of minimal microsatellite shift, 12 cases of EMC showed minimal microsatellite shift including 8 cases of dMMR/MSS and 4 cases of dMMR/MSI-L and these cases were ultimately evaluated as dMMR/MSI-H. Then, 21.49% (49/228) of EMC showed MSI-H and the discordance rate MMR-IHC and MSI-PCR in EMC decreased to 6.58% (15/228). No minimal microsatellite shift was found in CRC. Compared with EMC group with major microsatellite shift, cases with minimal microsatellite shift showed younger age, better tumor differentiation, and earlier International Federation of Gynecology and Obstetrics (FIGO) stage. There were significant differences in histological variant and FIGO stage between the two groups (P < 0.001, P=0.006).@*CONCLUSION@#EMC was more prone to minimal microsatellite shift, which should not be ignored in the interpretation of MSI-PCR results. The combined detection of MMR-IHC and MSI-PCR is the most sensitive and specific method to capture MSI tumors.

Clinical application of PARP inhibitors in breast cancer / 国际肿瘤学杂志

Poly adenosine diphosphate ribose polymerase (PARP) inhibitors lead to synthetic lethality in homologous recombination repair-deficient (HRD) tumors by inhibiting DNA damage repair. Two PARP inhibitors, olaparib and talazoparib, have been approved for the salvage treatment of breast cancer susceptibility gene (BRCA) mutation, human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer, and adjuvant treatment of early breast cancer. PAPR inhibitor single agent shows good antitumor activity and controllable safety. A number of clinical studies on PAPR inhibitors combined with chemotherapy, radiotherapy, antiangiogenic therapy and immunotherapy are being carried out. The indications of PARP inhibitors also extend from BRCA mutation to HRD, from ovarian cancer and breast cancer to other solid tumors, promising to benefit more patients in the future.

Effects of apatinib on quality of life and immune function in older adult patients with advanced non-small cell lung cancer / 中国基层医药

Objective:To analyze the effects of apatinib on quality of life and immune function in older adult patients with advanced non-small cell lung cancer.Methods:A total of 187 older adult patients with advanced non-small cell lung cancer admitted to Taizhou Cancer Hospital from January 2017 to January 2021 were included in this study. They were divided into the control group ( n = 93) and the observation group ( n = 94). The control group was treated with carboplatin combined with pemetrexed and the observation group was treated with apatinib based on carboplatin and pemetrexed. Sign and symptoms remission was compared between the observation and control groups. The levels of tumor markers, immune function, and quality of life score were compared between the two groups before and after treatment. Results:Total remission rate in the observation group was significantly higher than that in the control group (88.30% vs. 69.89%, χ2 = 9.59, P < 0.05). After treatment, carbohydrate antigen 125, carbohydrate antigen 50, and carcinoembryonic antigen in the observation group were (16.25 ± 5.47) μg/L, (15.23 ± 3.27) μg/L and (5.91 ± 2.66) mg/L, respectively, which were significantly lower than (21.49 ± 6.61) μg/L, (19.11 ± 3.48) μg/L and (10.14 ± 2.73) mg/L in the control group ( t = 5.91, 7.86, 10.73, all P < 0.05). The percentage of CD3 + and CD4 + cells, and the ratio of CD4 +/CD8 + cells in the observation group were (69.34 ± 8.85)%, (38.15 ± 6.52)%, (1.40 ± 0.33), respectively, which were significantly higher than (64.51 ± 8.74)%, (33.55 ± 6.33)%, (1.23 ± 0.25) in the control group ( t = -3.75, -5.36, -3.97, all P < 0.05). Quality of life score was increased in each group ( P < 0.001). The amplitude of increase in quality of life score was greater in the observation group compared with the control group ( P < 0.001). Conclusion:Apatinib can effectively reduce the level of tumor markers and improve immune function in older adult patients with advanced non-small cell lung cancer and improve quality of life.

The value of IGFBP1 in the diagnosis and prognosis of nasopharyngeal carcinoma / 中国医师杂志

Objective:To explore the role of insulin-like growth factor binding protein 1 (IGFBP1) in the diagnosis and prognosis of nasopharyngeal carcinoma (NPC), and to search for molecular markers that can be used for the diagnosis of NPC.Methods:A retrospective analysis was conducted on 150 NPC patients (treated from April 2014 to May 2015) at the Cancer Hospital Affiliated to Shantou University Medical School, and clinical baseline data were collected from 143 healthy individuals (normal control group) during the same period. The serum IGFBP1 concentration was detected using enzyme-linked immunosorbent assay (ELISA) in 112 nasopharyngeal carcinoma patients and 109 normal controls in the training cohort, and was validated in the validation cohort (38 nasopharyngeal carcinoma patients and 34 normal controls). The diagnostic value of serum IGFBP1 in nasopharyngeal carcinoma was evaluated using the receiver operating characteristic curve (ROC).Results:Compared to the normal control group, the expression level of serum IGFBP1 in nasopharyngeal carcinoma patients was higher in the training and validation queues (all P<0.05). In the training queue, the area under the ROC curve was 0.768 (95% CI: 0.706-0.830), with diagnostic specificity and sensitivity of 90.83% and 48.21%, respectively. In the validation queue, the area under the ROC curve was 0.798 (95% CI: 0.697-0.899), with diagnostic specificity and sensitivity of 97.06% and 31.58%, respectively. The predictive values for positive cases in both cohorts were greater than 80%, while the predictive values for negative cases were greater than 50%. The diagnostic threshold for serum IGFBP1 in both cohorts was 1 077 ng/ml. Conclusions:IGFBP1 has practical value as a molecular marker for the diagnosis of nasopharyngeal carcinoma.

18F-FDG PET/CT combined with tumor markers for diagnosis of non stage ⅠA limited-stage small cell lung cancer / 中国医学影像技术

Objective To observe the value of 18F-FDG PET/CT combined with tumor markers for diagnosis of non stageⅠ A limited-stage small cell lung cancer(LS-SCLC).Methods Totally 87 cases of non stage Ⅰ A LS-SCLC(LS-SCLC group),137 of non stage Ⅰ A non-small cell lung cancer(NSCLC,NSCLC group)and 48 cases of pulmonary inflammatory lesions(inflammatory group)were enrolled.Patients'general data,tumor marker levels and PET/CT findings were comparatively analyzed.Logistic regression analysis was performed to evaluate the efficacy of parameters for diagnosing non stage Ⅰ A LS-SCLC.Results There were significant differences of patients'age,neuron-specific enolase(NSE),pro-gastrin-releasing peptide(ProGRP),carcinoembryonic antigen(CEA),squamous cell carcinoma antigen(SCCA)and cytokeratin-19-fragment(CYFRA21-1),as well as of the maximum lesion diameter,maximum standard uptake value(SUVmax),morphology,spiculation sign,relationship between long axis and bronchus,lymph node fusion and proportion of lymph node with higher SUVmax than primary lesion among 3 groups(all P＜0.05).The area under the curve(AUC)of the combination of spiculation sign,NSE＞23.5 μg/L,ProGRP＞111.8 ng/L,SCCA≤2.5 μg/L and CYFRA21-1≤7.4 μg/L for differentiating LS-SCLC and NSCLC was 0.91,higher than that of each single parameter(all P＜0.05).AUC of the combination of SUVmax＞8.1,NSE＞19.4 μg/L,ProGRP＞72.5 ng/L and lymph node fusion for differentiating LS-SCLC and pulmonary inflammatory lesions was 0.99,higher than each single parameter(all P＜0.05).Conclusion 18F-FDG PET/CT combined with tumor markers ProGRP and NSE was helpful for diagnosing non stage ⅠA LS-SCLC.

Expressão de enzimas modificadoras de MRNA no carcinoma renal de células claras e no carcinoma de mama / Expression of MRNA-modifying enzymes in clear cell renal cell carcinoma and breast cancer

Após a transcrição, as moléculas de RNA podem ser alteradas por uma infinidade de modificações químicas distintas que ocorrem de maneira dinâmica, constituindo o epitranscriptoma. A primeira modificação de mRNA identificada foi a N6-metiladenosina (m6A), afetando quase todas as etapas do metabolismo do RNA, desde o processamento no núcleo até a tradução e decaimento no citoplasma, alterando assim os níveis de expressão gênica. A m6A é controlada por três grupos de proteínas, writers, readers e erasers. Na literatura estudos relatam que as proteínas que regulam a m6A possam estar mutadas e / ou exibir expressão alterada através de uma variedade de tipos de tumores, mais notavelmente o carcinoma de mama e o CRCC. Neste projeto, tivemos como objetivo determinar os níveis de expressão das enzimas modificadoras de mRNA, e suas correlações com dados clínicos e anatomopatológicos para CRCC e carcinoma de mama, o que pode nos ajudar a ampliar o conhecimento sobre os mecanismos moleculares associados a estas doenças. Em nossa coorte dos pacientes com CRCC, detectamos que a baixa expressão da writer RBM15B, se associa com variáveis relacionadas a progressão tumoral e apresenta pior SR e aumento de risco do paciente recidivar. A baixa expressão da FTO e alta da METTL14, se associam aos estágios mais agressivos de CRCC, podendo serem possíveis marcadores de prognóstico. No carcinoma de mama, os pacientes com expressão baixa da METTL14, apresentaram associação com pior prognóstico para esta doença, especificamente no subtipo molecular TN e aumento de risco em (RR = 4,772; p= 0,01), para óbito global. Sendo assim, acreditamos que interferência no mecanismo de controle da m6A no mRNA desencadeada por alterações de expressão destas proteínas, podem estar ligadas a alterações biológicas levando ao processo de tumorigênese

After transcription, RNA molecules can be altered by a multitude of different chemical modifications that occur dynamically, constituting the epitranscriptome. The first mRNA modification identified was N6-methyladenosine (m6A), affects almost all steps of RNA metabolism, from processing in the nucleus to translation and decay in the cytoplasm, thus altering gene expression levels. m6A is controlled by three groups of proteins, writers, readers and erasers. Studies in the literature report that proteins that regulate m6A may be mutated and/or exhibit altered expression across a variety of tumor types, most notably breast cancer and ccRCC. In this project, we aimed to determine the expression levels of mRNA-modifying enzymes, and their correlations with clinical and anatomopathological data for ccRCC and breast cancer, which can help to expand our knowledge about the molecular mechanisms associated with these diseases. In our cohort of patients with ccRCC, we detected that the low expression of writer RBM15B is associated with characteristics related to tumor progression showing worse Relapse-Free survival and increased recurrence risk. Low expression of FTO and high expression of METTL14 are associated with more aggressive stages of ccRCC and may be possible prognostic markers. In breast cancer, patients with low METTL14 expression were associated with a worse prognosis, specifically in the TN molecular subtype, with increased death risk (RR = 4.772; p= 0.01). Therefore, we believe that interference in the m6A control mechanism in the mRNA triggered by changes in the expression of these proteins may be linked to biological alterations leading to the process of tumorigenesis

Value of different tumor markers for the diagnosis and prognosis prediction of colon cancer in patients / 中国基层医药

Objective:To comprehensively analyze the clinical values of serum tumor markers of colon cancer, including carbohydrate antigen 724 (CA724), cytokeratin 19 fragment antigen (CYFRA21-1), carbohydrate antigen199 (CA199) and carcinoembryonic antigen (CEA) in the diagnosis and prognosis prediction of colon cancer in patients.Methods:The clinical data of 160 patients with colon cancer who received treatment in Zhuji Central Hospital from January 2018 to December 2020 (observation group) and the clinical data of 156 patients with benign colon polyps who concurrently received physical examination (control group) were retrospectively analyzed. All patients underwent CA724, CYFRA21-1, CA199 and CEA tumor marker screening. The levels of tumor markers, the positive rate of a single tumor marker, and the positive rate of a combination of four markers were compared between the control and observation groups. The levels of tumor markers were compared among different pathological stages. The levels of serum tumor markers were compared among patients with different prognoses based on 1-year follow-up data.Results:CA199-positve rate, CEA-positive rate, CYFRA21-1-positve rate, CA724-positive rate, and the positive rate of a combination of four tumor markers were 85.63% (137/160), 86.88% (139/160), 71.88% (115/160), 85.00% (136/160), and 95.63%(153/160), respectively, which were significantly higher than those in the control group ( χ2 = 8.64, 10.28, 8.33, 9.93, 7.27, all P < 0.001). Serum CA199, CEA, CYFRA21-1 and CA724 levels in patients with stage III-IV colon cancer were (58.96 ± 13.59) U/mL, (38.69 ± 11.84) μg/L, (14.78 ± 3.68) μg/L, (23.68 ± 5.38) U/mL, respectively, which were significantly higher than those in patients with stage I-II colon cancer [(48.35 ± 9.03) U/mL, (23.96 ± 12.25) μg/L, (9.57 ± 2.53) μg/L, (13.02 ± 4.32) U/mL, t = 10.29, 12.02, 8.47, 10.54, all P < 0.001). One-year follow-up results showed that serum levels of CA199, CEA, CYFRA21-1, CA724 in patients with recurrence and metastasis of colon cancer were (38.68 ± 3.04) U/mL, (17.12 ± 4.96) μg/L, (8.94 ± 2.32) μg/L, (11.22 ± 1.94) U/mL, which were significantly higher than those in patients without recurrence of colon cancer [(30.02 ± 2.95) U/mL, (3.75 ± 1.06) μg/L, (3.06 ± 1.15) μg/L, (6.28 ± 1.53) U/mL, t = 8.73, 11.02, 7.72, 7.57, all P < 0.001]. Conclusion:Serum levels of CEA, CA199, CA724 and CYFRA21-1 can be used as important indicators for diagnosis and prognosis prediction of colon cancer.

Peripheral blood circular RNA circ_0141633 and circ_0008234 as potential diagnostic and prognostic biomarkers in pancreatic cancer / 中国医师杂志

Objective:To clarify the clinical significance, diagnostic and prognostic values of circular RNA circ_0141633 and circ_0008234 in peripheral blood of pancreatic cancer, and analyze their impact on the biological function of pancreatic cancer cells.Methods:The peripheral blood samples of 97 pancreatic cancer patients and 71 healthy controls were collected, and the expression of circ_0141633 and circ_0008234 was analyzed by real-time quantitative polymerase chain reaction (qRT-PCR). The relationships between the expression of circ_0141633 and circ_0008234 and clinicopathological characteristics and prognosis of pancreatic cancer were analyzed by chi-square test, K-M survival curves and Cox proportional hazards regression model. The area under curve (AUC), sensitivity and specificity of circ_0141633 and circ_0008234 in the diagnosis of pancreatic cancer were analyzed by receiver operating characteristic (ROC) curve. The effects of circ_0141633 and circ_0008234 on the proliferation, migration, invasion and epithelial mesenchymal transformation (EMT) of Bxpc-3 cells were analyzed by methyl thiazolyl tetrazolium (MTT) method, cell scratch test, Transwell invasion and Western blot.Results:The expression of circ_0141633 and circ_0008234 in peripheral blood of pancreatic cancer patients was higher than those of healthy controls (all P<0.05). High expression of circ_0141633 and circ_0008234 was associated with higher clinical stage, lymph node metastasis and venous invasion, and were independent risk factors for poor prognosis in pancreatic cancer (all P<0.05). The overall survival rate of patients with high expression of circ_0141633 and circ_0008234 was significantly lower than that of patients with low expression of circ_0141633 and circ_0008234 (all P<0.05). The AUC of circ_0141633, circ_0008234, the combination of circ_0141633 and circ_0008234, CA19-9 in the diagnosis of pancreatic cancer was 0.70, 0.67, 0.88 and 0.82, with sensitivity of 64.32%, 60.79%, 78.22% and 73.97%, respectively. The specificity was 68.54%, 65.46%, 81.65% and 79.41%, respectively. The diagnostic efficiency of combination was superior to CA19-9, circ_0141633 and circ_0008234 alone (all P<0.05). Interfering with circ_0141633 and circ_0008234 alone could inhibit the proliferation, migration, invasion and EMT of Bxpc-3 cells, and the above inhibitory effect was more obvious after interfering with both of circ_0141633 and circ_0008234 (all P<0.05). Conclusions:The high expression of circ_0141633 and circ_0008234 in peripheral blood could be used as potential diagnostic and prognostic biomarkers of pancreatic cancer, and could promote the progression of pancreatic cancer.

The value of CD3G expression in the prediction of efficacy of anti-PD-1/PD-L1 immunotherapy for non-small cell lung cancer / 中国基层医药

Objective:To explore the markers predicting the efficacy of anti-programmed death receptor-1 (PD-1)/PD-1 ligand (PD-L1) immunotherapy for non-small cell lung cancer (NSCLC) and analyze their relationships with the tumor immune microenvironment.Methods:(1) Gene expression profile data and relevant clinical data of 55 NSCLC patients receiving anti-PD-1/PD-L1 monotherapy from two independent clinical cohorts were downloaded from the GEO database. Genes associated with progression-free survival (PFS) were screened using univariate Cox regression analysis. (2) Twenty-six pathological tissue specimens of NSCLC patients who received anti-PD-1/PD-L1 monotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences (CICAMS) from April 2016 to August 2019 prior to the screening of genes were selected to verify the predictive value of the screened genes using immunohistochemistry. (3) The relationship between efficacy predictive markers and PD-L1 and infiltrating immune cells in the tumor immune microenvironment was analyzed using NSCLC gene expression profile downloaded from the TCGA database.Results:Univariate Cox regression analysis revealed that only T-Cell Surface Glycoprotein CD3 Gamma Chain (CD3G) was a risk predictive gene for PFS in NSCLC patients in both clinical cohorts of the GEO database (GSE93157: P = 0.049; GSE136961: P = 0.034). Further Kaplan-Meier survival curves showed that PFS was significantly prolonged in the high CD3G expression group ( P = 0.012). The results of survival analysis in the CICAMS clinical cohort also demonstrated that NSCLC patients with high CD3G expression had a better prognosis after receiving anti-PD-1/PD-L1 monotherapy ( P = 0.001) compared with those with low CD3G expression. Univariate and multivariate Cox regression analyses also showed that CD3G was an independent predictor of PFS (univariate: P = 0.002; multivariate: P = 0.001). The tumor immune microenvironment analysis showed that CD3G was positively correlated with PD-L1 expression (lung adenocarcinoma: r = 0.44, P < 0.001; lung squamous cell carcinoma: r = 0.37, P < 0.001) and the infiltration level of CD8 + T cells (lung adenocarcinoma: r = 0.13, P = 0.002; lung squamous cell carcinoma: r = 0.70, P < 0.001). CD3G was also positively correlated with the expression of CD8 + T cell chemokines CCL5, CXCL9, CXCL10 and CXCL11. Conclusion:Patients with NSCLC with high CD3G expression have greater clinical benefits after anti-PD-1/PD-L1 monotherapy compared with those with low CD3G expression. CD3G can be used as a potential marker to predict the efficacy of immunotherapy for NSCLC.

Clinical effect of anti-PD-1/PD-L1 immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced cervical cancer / 中国医师杂志

Objective:To investigate the clinical effect of programmed death receptor-1 (PD-1)/programmed death receptor ligand-1 (PD-L1) immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced cervical cancer (LACC).Methods:From November 2018 to October 2019, 51 LACC patients in Qinhuangdao First Hospital who received anti-PD-1/PD-L1 immunotherapy (pembrolizumab) combined with concurrent radiotherapy and chemotherapy [intensity modulated radiotherapy (IMRT)+ TP (taxol+ carboplatin) chemotherapy] were selected as the observation group. 51 LACC patients who received concurrent chemotherapy and radiotherapy were selected as the control group. The objective remission rate, disease control rate, tumor markers [squamous cell carcinoma antigen (SCCAg), soluble cytokeratin 19 fragment (CYFRA21-1), and carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125)], proliferation and apoptosis indicators [survivin (Survivin), B-cell lymphoma-2 (Bcl-2), Caspase-3 (Caspase-3), apoptosis-promoting substance (Bax)], PD-1/PD-L1 [soluble PD-L1 (sPD-L1), CD4 + T cell surface PD-1 expression (PD-1 CD4 + T cells), CD8 + T cell surface PD-1 expression (PD-1 CD8 + T cell) and CD14 + monocyte surface PD-L1 expression (PD-L1 CD14 + monocyte)], safety and survival rate within 1 year were compared between the two groups. Results:(1) Disease control and safety: the objective response rate and disease control rate of the observation group were 80.39%(41/51) and 92.16%(47/51), respectively, which were higher than those of the control group by 39.22%(20/51) and 70.59%(36/51) (all P<0.05), but there was no significant difference in the incidence of side effects between the groups (all P>0.05). (2) Tumor markers and proliferation and apoptosis indexes: compared with those before treatment, the levels of serum SCCAg, CYFRA21-1, CEA, CA125, survivin and Bcl-2 in the two groups after treatment were significantly lower, and the levels of Caspase-3 and Bax were significantly higher; the above indexes in the observation group were better than those in the control group after treatment (all P<0.05). (3) PD-1/PD-L1: after treatment, sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells and PD-L1 CD14 + monocytes in the observation group were significantly lower than those before treatment (all P<0.05). After treatment, the sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells, PD-L1 CD14 + monocytes in the observation group were lower than those in the control group (all P<0.05). (4) Survival: the survival rate of the observation group was higher than that of the control group within 1 year ( P<0.05). Conclusions:The clinical effect of anti-PD-1/PD-L1 immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of LACC is significant. It can effectively inhibit the progression of the disease by regulating tumor markers, proliferation and apoptosis indicators and PD-1/PD-L1 expression without increasing the risk of treatment, and has a positive effect on improving the survival rate of patients.