Construction and Verification of A Nomogram Model for Predicting Invasive Risk of Ground Glass Nodules / 肿瘤防治研究

Objective To investigate the importance of a nomogram model based on biomarkers and CT signs in the prediction of the invasive risk of ground glass nodules. Methods A total of 322 patients with ground glass nodule, including 240 and 82 patients in the model and verification groups, respectively, were retrospectively analyzed. Independent risk factors for the invasive risk of ground glass nodules were screened out after using single and multiple Logistic analysis. R software was used to construct the nomogram model, and clinical decision curve analysis (DCA), receiver operating curve (ROC), and calibration curve were used for internal and external verification of the model. Results In this study, the independent risk factors for the invasive risk of ground glass nodules included systemic immune-inflammation index (SII), CYFRA21-1, edge, vascular cluster sign, and nodular consolidation tumor ratio (CTR). The area under the ROC curve of the constructed nomogram model had a value of 0.946, and that of the external validation group reached 0.932, which suggests the good capability of the model in predicting the invasive risk of ground glass nodules. The model was internally verified through drawing of calibration curves of Bootstrap 1000 automatic sampling. The results showed that the consistency index between the model and actual curves reached 0.955, with a small absolute error and good fit. The DCA curve revealed a good clinical practicability. In addition, nodule margin, vascular cluster sign, and CTR were correlated with the grade of pathological subtype of invasive adenocarcinoma. Conclusion A nomogram model based on biomarkers and CT signs has good value and clinical practicability in the prediction of the invasive risk of ground glass nodules.

Construction of micropapillary lung adenocarcinoma organoids and screening of targeted drugs / 天津医药

Objective To establish a culture method for micropapillary lung adenocarcinoma organoids and conduct targeted drug screening.Methods Organoids were extracted and cultured from a surgical tissue sample of a patient diagnosed with micropapillary lung adenocarcinoma,and the growth of lung cancer organoids was observed and recorded dynamically.The morphological and gene expression characteristics of tumor cells between lung cancer organoids and parental tissue were compared using hematoxylin eosin(HE)staining and immunohistochemical methods.Real time fluorescence quantitative polynucleotide chain reaction(qRT-PCR)method was used to detect gene mutations in lung cancer parental tissue and organoids.Finally,based on results of genetic testing,targeted drugs were selected and their therapeutic effects were verified.Results We have successfully cultured spherical organoids from micropapillary lung adenocarcinoma tissue,which can be passaged for at least 3 generations.HE staining results showed that the morphology of tumor cells in organoids was roughly consistent with that of parental tissue.The immunohistochemical results showed that the protein expression levels of various genes in lung cancer organoids and parental tissue were roughly the same.Results of gene mutation analysis showed that the mutated genes in lung cancer parental tissue and organoids were consistent,both reflecting RET fusion.The screening results of targeted drugs based on lung cancer organoids showed that vandertinib had the best anti-tumor effect in vitro.Conclusion Drug screening experiments based on micropapillary lung adenocarcinoma organoids can screen highly efficient targeted drugs in a short period of time,which may benefit patients with micropapillary lung adenocarcinoma.

Construction of a predictive model for the prognosis of elderly patients with advanced lung adenocarcinoma after surgery based on the SEER database / 肿瘤研究与临床

Objective:To construct and analyze the visual nomogram predictive model for the prognosis of elderly advanced lung adenocarcinoma patients after surgery based on the Surveillance, Epidemiology, and End Results (SEER) database.Methods:SEER*Stat8.4.0.1 software was used to screen out the data from 17 register in SEER database between 2000 and 2019, and finally 4 453 lung adenocarcinoma patients aged ≥ 65 years who underwent surgical treatment and were diagnosed as stage Ⅲ and Ⅳ according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging criteria were enrolled. The data were randomly divided into the training set (3 117 cases) and the validation set (1 336 cases) in a 7:3 ratio; the epidemilogical data and clinicopathological characteristics of the two groups were compared. LASSO regression was used for data dimensionality reduction to select the best predictors from the prognostic factors of patients. Cox proportional risk model was used to perform univariate and multivariate analyses of the screened variables, and based on R software rms package and the prognostic independent risk factors, the nomogram was constructed to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) rates of the patients. The validation set was validated by using Bootstrap method with 1 000 equal repeated samples with playback, and the accuracy of the nomogram model was verified by using the C-index, receiving operating characteristic (ROC) curves and calibration curves.Results:There were no statistically significant differences in age, gender, race, tumor location, Grade grading, surgery methods, the number of lymph node dissection, radiotherapy, tumor diameter, tumor metastasis, marriage, living condition, TNM staging, radiochemotherapy of training set and validation set (all P > 0.05). In training set, 18 variables were included into LASSO regression analysis and were performed with dimensionality reduction; ultimately, 11 optimal predictive variables were selected, including age ≥ 85 years ( HR = 2.34, 95% CI: 1.803-3.037, P < 0.01), male ( HR = 1.326, 95% CI: 1.228-1.432, P < 0.01), Grade grading Ⅲ-Ⅳ ( HR = 1.333, 95% CI: 0.844-2.105, P < 0.01), undissected lymph nodes ( HR = 2.261, 95% CI: 2.023-2.527, P < 0.01), tumor diameter ≥3.7 cm ( HR = 1.445, 95% CI: 1.333-1.566, P < 0.01), bone metastasis ( HR = 1.535, 95% CI: 1.294-1.819, P < 0.01), brain metastasis ( HR = 1.308, 95% CI: 1.117-1.532, P < 0.01), lung metastasis ( HR = 1.229, 95% CI: 1.056-1.431, P = 0.01), living in rural areas ( HR = 1.215, 95% CI: 1.084-1.363, P < 0.01), TNM staging Ⅳ ( HR = 1.155, 95% CI: 1.044-1.278, P = 0.01), postoperative radiotherapy ( HR = 1.148, 95% CI: 1.054-1.250, P < 0.01); lung adenocarcinoma patients with the above 11 factors had worse prognosis. Based on the variables, the nomogram predictive model was constructed to predict 1-, 3-, and 5-year CSS rates of elderly advanced lung adenocarcinoma patients. Bootstrap method was used for repeated sampling for 1 000 times to verify the modeling effect of nomogram. In the model group, C-index was 0.654 (95% CI: 0.641-0.668), 0.666 (95% CI: 0.646-0.685), respectively in the training set and the validation set. The nomogram was drawn to predict ROC curves of 1-, 3-, and 5-year CSS rates for elderly advanced lung adenocarcinoma patients after operation in the training set and validation set; the area under the curve (AUC) of 1-year, 3-year, and 5-year CSS rates was 0.730 (95% CI: 0.708-0.754) and 0.689 (95% CI: 0.672-0.710), 0.687 (95% CI: 0.668-0.711) and 0.731 (95% CI: 0.697-0.765), 0.712 (95% CI:0.684-0.740) and 0.714 (95% CI: 0.683-0.745), respectively in the training and validation sets. The calibration curve showed a high consistency between the predicted probability of the model and the actual probability. Conclusions:The nomogram model constructed by optimal predictive variables for predicting the prognosis of elderly advanced lung adenocarcinoma patients after surgery may be a convenient tool for survival prediction of these patients.

Progress of diagnosis, treatment and prognosis in lung micropapillary adenocarcinoma / 肿瘤研究与临床

The incidence of lung micropapillary adenocarcinoma is low, and it is easy to relapse and metastasize after operation, which leads to poor prognosis. This article mainly summarizes the imaging and histopathological features of lung micropapillary adenocarcinoma and discusses the effects of surgical procedures, chemotherapy and targeted drug therapy on the prognosis of patients, in order to deepen the understanding of lung micropapillary adenocarcinoma.

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.

Pemetrexed clinical trial for intrathecal injection chemotherapy based on cerebrospinal fluid pharmacokinetics in patients with leptomeningeal metastasis from lung adenocarcinoma / 国际肿瘤学杂志

Objective:To investigate the pharmacokinetics of cerebrospinal fluid pemetrexed following intrathecal injection chemotherapy in patients with leptomeningeal metastasis (LM) from lung adenocarcinoma and provide a basis for clinical intrathecal injection chemotherapy.Methods:A total of 21 patients with lung adenocarcinoma LM who underwent pemetrexed intrathecal injection chemotherapy via Ommaya capsule at Nanjing Drum Tower Hospital, Aiffilitated Hospital of Nanjing University Medical School from November 2019 to November 2022 were collected, and divided into 30, 40 and 50 mg groups ( n=10, n=4, n=7) according to pemetrexed dose. Cerebrospinal fluid was collected at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy, and day 8 of each cycle for three groups. Reversed phase high performance liquid chromatography was used to determine the drug concentration in cerebrospinal fluid, to clarify the drug-related pharmacokinetic parameters, and to compare the differences in pemetrexed concentration among groups. Finally, cerebrospinal fluid pemetrexed concentration changes were observed and compared after different intrathecal injection chemotherapy cycles. Results:There were statistically significant differences in cerebrospinal fluid drug concentrations of patients in three groups at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy (30 mg group: F=20.56, P<0.001; 40 mg group: F=27.06, P<0.001; 50 mg group: F=28.63, P<0.001), and there were statistically significant differences in the concentration of cerebrospinal fluid drugs in each dose group at 0.5, 1, 2, 4, 6 and 12 h compared to 0 h after intrathecal injection chemotherapy (all P<0.05). Compared to the 30 mg group, cerebrospinal fluid drug concentrations in the 50 mg group increased at 1, 2, 4, 6, 12 and 24 h after intrathecal injection chemotherapy, with statistically significant differences (all P<0.05). Pharmacokinetic analysis of cerebrospinal fluid pemetrexed showed that area under the concentration-time curve (AUC) 0-∞ of the 30, 40 and 50 mg groups were (5 696.12±283.32), (7 886.29±396.57), and (14 202.70±440.19) h·mg/L, respectively, with a statistically significant difference ( F=1 159.00, P<0.001) ; AUC 0-∞ increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; AUC 0-∞ increased in the 40 mg group compared to the 30 mg group ( P<0.05). The half-lives of three groups were (8.75±0.23), (11.29±0.59) and (16.42±1.23) h, respectively, with a statistically significant difference ( F=206.80, P<0.001) ; half-life was longer in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; half-life was longer in the 40 mg group compared to the 30 mg group ( P<0.05). The peak time of three groups were (1.55±0.10), (1.00±0.01), (1.43±0.11) h, respectively, with a statistically significant difference ( F=48.11, P<0.001) ; the peak time was shorter in the 40 and 50 mg groups compared to the 30 mg group (both P<0.05). Clearance of three groups were (7.02±2.46), (5.80±1.25) and (3.66±1.32) L/h, respectively, with a statistically significant difference ( F=6.02, P=0.009) ; clearance was decreased in the 50 mg group compared to the 30 mg group ( P<0.05). The peak concentration of three groups were (540.45±32.25), (820.75±46.47) and (1 014.78±64.96) mg/L, respectively, with a statistically significant difference ( F=207.70, P<0.001) ; peak concentration increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; peak concentration increased in the 40 mg group compared to the 30 mg group ( P<0.05). Cerebrospinal fluid drug concentrations were dynamically monitored after 4 cycles of intrathecal injection chemotherapy, in which cerebrospinal fluid pemetrexed concentrations in 30 mg group were (13.76±4.79), (11.41±7.08), (9.41±2.59) and (7.86±4.02) mg/L, respectively; 40 mg group were (14.45±6.59), (12.87±15.73), (11.24±2.48) and (9.09±3.38) mg/L, respectively; 50 mg group were (12.94±10.34), (9.72±7.62), (8.15±8.17) and (4.34±4.21) mg/L, respectively. There was a statistically significant difference in cerebrospinal fluid drug concentrations among different intrathecal injection chemotherapy cycles in 30 mg group ( F=4.04, P=0.016), and the cerebrospinal fluid drug concentration decreased in cycles 3 and 4 compared to cycle 1 (both P<0.05). There were no statistically significant differences in cerebrospinal fluid drug concentrations among different treatment cycles in 40 and 50 mg groups ( F=0.28, P=0.837; F=3.57, P=0.066) . Conclusion:Reversed phase high performance liquid chromatography method can effectively detect the pemetrexed concentration in cerebrospinal fluid; dynamic monitoring of cerebrospinal fluid pemetrexed concentration can provide a basis for the dosage and the treatment cycle of intrathecal injection chemotherapy in LM patients with lung adenocarcinoma.

Study on the inhibitory effect of UBE2T on radiosensitivity of lung adenocarcinoma / 中华放射肿瘤学杂志

Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.

Correlations of β-catenin expression with clinical efficacy of tyrosine kinase inhibitors and prognosis of advanced lung adenocarcinoma patients with epidermal growth factor receptor mutations / 肿瘤研究与临床

Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm: χ2 = 3.99, P = 0.046,ectopic expression in nucleus: χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS: HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS: HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.

Study on prediction of potential targets and mechanism of Zeqi Decoction in the treatment of lung adenocarcinoma / 国际中医中药杂志

Objective:To explore the potential molecular targets and mechanism of Zeqi Decoction in the treatment of lung adenocarcinoma (LUAD) through bioinformatics and cell experiment.Methods:The active components of Zeqi Decoction were collected based on TCMSP database and literature search. Then R software was used to screen differentially expressed genes in LUAD from TCGA and GEO databases. The co-expression module was obtained through weighted gene co-expression network analysis (WGCNA), and the potential targets were obtained after matching and mapping with targets of Zeqi Decoction. Enrichment analysis of GO function and KEGG pathway of targets was conducted. The results were experimentally verified. The lung adenocarcinoma cell lines A549 and H1299 were divided into blank control group and Zeqi Decoction group according to random number table. The inhibition rate of cell proliferation was detected by cell proliferation test (CCK-8); the expression of leukocyte differentiation antigen 36 (CD36) in A549 and H1299 cells was detected by Western blot; the levels of low density lipoprotein receptor (LDLR) and IL-6 were detected by ELISA.Results:Totally 157 anti-lung adenocarcinoma active components and 18 potential targets were obtained, mainly including CD36, IL6, LDLR, etc. The main target of Zeqi Decoction in the treatment of lung adenocarcinoma was lipid metabolism. The results showed that Zeqi Decoction could effectively inhibit the activity of A549 and H1299 cells and the levels of CD36, LDLR and IL-6.Conclusion:Zeqi Decoction can inhibit the inflammatory response by down-regulating the protein expressions of CD36 and LDLR, thereby slowing the proliferation of cells.

Research progress in the mechanism of TCM intervention in anti-tumor effect of A549 cells in human lung adenocarcinoma / 国际中医中药杂志

Traditional Chinese Medicine (TCM) exerts anti-tumor effects by intervening in A549 cells of human lung adenocarcinoma, mainly including activating or inhibiting downstream target proteins of Bcl-2 and Bax, or forming RIP1/RIP3/MLKL complex bodies by affecting pathways such as PI3K/Akt, thereby inducing apoptosis in A549 cells of lung adenocarcinoma; blocks the cell growth phase, thereby inhibiting the proliferation of lung adenocarcinoma A549 cells; inhibits invasion and metastasis of A549 cells by affecting the MMPs pathway, STAT3 pathway, and regulating epithelial mesenchymal transition related factors; suppresses or activates the expression of related proteins or affect related signaling pathways, thereby reversing the resistance of lung cancer A549/DDP cell lines to cisplatin and paclitaxel.

Características clínicas epidemiológicas de los pacientes con cáncer de pulmón en la provincia Camagüey 2017-2021

Introducción: El cáncer de pulmón es una de las enfermedades más graves y uno de los cánceres con mayor incidencia en las personas, responsable de los mayores índices de mortalidad oncológica a escala mundial. Objetivo: Analizar las características clínicas epidemiológicas de los pacientes con cáncer de pulmón. Métodos: Se realizó un estudio observacional descriptivo retrospectivo, con el objetivo de analizar las características clínicas epidemiológicas de los pacientes con el diagnóstico de cáncer de pulmón atendido en el Hospital Oncológico María Curie durante el quinquenio de enero de 2017 a diciembre de 2021. El universo de estudio incluyó a los 822 pacientes que fueron atendidos en el hospital durante el período antes señalado, con cáncer de pulmón. La muestra a discreción la conformaron 276 pacientes. Resultados: Predominio del cáncer de pulmón en los pacientes de 61 a 80 años de edad, sexo masculino, fumadores pasivos. La variedad cito-histológica con mayor incidencia fue el carcinoma de células pequeñas microcítico; debut de esta enfermedad en pacientes en estadio IV y con tratamiento recibido de radioterapia y quimioterapia en el 100 % de los pacientes. Conclusiones: Es un tumor predominante entre las neoplasias malignas, donde el diagnóstico oportuno permite tratar en estadios tempranos, lo cual favorece la sobrevida en pacientes.

Introduction: Lung cancer is one of the most serious diseases and one of the cancers with the highest incidence in people, responsible for the highest oncological mortality rates worldwide. Objective: To analyze the clinical-epidemiological characteristics of patients with lung cancer. Methods: A retrospective descriptive observational study was carried out, with the objective of analyzing the epidemiological clinical characteristics of patients diagnosed with lung cancer treated at the María Curie Oncological Hospital during the five-year period from January 2017 to December 2021. The universe of study included 822 patients who were treated in the hospital during the aforementioned period with lung cancer. The sample at discretion was made up of 276 patients. Results: Prevalence of lung cancer in patients between 61 and 80 years of age, male, passive smokers. The cyto-histological variety with the highest incidence was small cell microcytic carcinoma; debut of this disease in patients in stage IV and with treatment received with radiotherapy and chemotherapy in 100% of the patients. Conclusions: It is a predominant tumor among malignant neoplasms, where timely diagnosis allows treatment in early stages, which favors survival in patients.

SAMHD1 inhibits PD-L1 expression in lung adenocarcinoma cells / 国际肿瘤学杂志

Objective:To explore the correlation between SAM domain and HD domain-containing protein 1 (SAMHD1) and programmed death-ligand 1 (PD-L1) expression in lung adenocarcinoma.Methods:The expression of SAMHD1 in lung adenocarcinoma and its effect on prognosis were analyzed by online database GEPIA and Kaplan-Meier Plotter. The expression of SAMHD1 in lung adenocarcinoma cell lines was detected by quantitative real-time PCR (qPCR) and Western blotting. SAMHD1 gene was silenced in H1975, H1299 and LLC cells by small interfering RNA transfection and lentivirus infection, respectively. The mRNA and protein expression levels of PD-L1 in lung adenocarcinoma cells of control group, siSAMHD1-1 group and siSAMHD1-2 group were detected by qPCR and Western blotting. The membrane PD-L1 level was detected by flow cytometry. A mouse lung adenocarcinoma xenograft model was constructed. The PD-L1 levels in the tumor tissues of control group and shSAMHD1 group were detected by immunohistochemistry. Cell proliferation activities of the control, siSAMHD1-1 and siSAMHD1-2 groups were detected by CCK-8 assays.Results:The GEPIA database results showed that the mRNA expression of SAMHD1 in lung adenocarcinoma was lower than that in normal lung tissue (4.81±0.90 vs. 5.99±0.76, t=20.67, P<0.001) . The median overall survival time of patients with high SAMHD1 expression was significantly longer than that of patients with low SAMHD1 expression (109.0 months vs. 87.7 months, χ2=26.83, P=0.002) . The relative mRNA expression levels of SAMHD1 in A549, PC9, H1299 and H1975 cells were 1.00±0.02, 0.75±0.05, 3.49±0.19 and 7.25±0.38 ( F=589.00, P<0.001) , and the relative protein expression levels were 1.00±0.06, 0.34±0.07, 1.67±0.22 and 2.11±0.63 ( F=15.79, P=0.001) . In H1975 cells, the relative mRNA levels of PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 1.00±0.00, 1.54±0.26 and 2.89±0.13 ( F=102.30, P<0.001) , and the relative protein expression levels were 1.00±0.01, 1.50±0.10 and 1.52±0.33 ( F=6.65, P=0.030) . In H1299 cells, the relative mRNA levels of PD-L1 in the three groups were 1.00±0.08, 1.63±0.03 and 2.14±0.03 ( F=368.80, P<0.001) , and the relative protein levels of PD-L1 were 1.00±0.07, 1.88±0.35 and 2.05±0.38 ( F=10.66, P=0.011) . The expression level of PD-L1 in the siSAMHD1-1 and siSAMHD1-2 groups was higher than that in the control group (all P<0.05) . Flow cytometry results showed that in H1975 cells, the fluorescence intensity of membrane PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 246.83±27.59, 325.60±8.00 and 308.93±7.60 ( F=17.56, P=0.003) , and in H1299 cells, the fluorescence intensity of membrane PD-L1 in the three groups were 959.00±6.25, 1 084.33±7.64 and 1 085.33±21.22 ( F=86.74, P<0.001) . The fluorescence intensity of PD-L1 in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . In xenograft mouse model, the H-SCORE of PD-L1 in the shSAMHD1 group was higher than that in the control group (7.99±1.10 vs. 4.49±0.43, t=5.13, P=0.007) . The proliferative activities of H1975 cells in the control group, siSAMHD1-1 group and siSAMHD1-2 group at 72 h were 0.50±0.02, 0.75±0.05 and 0.73±0.06 ( F=25.01, P=0.001) . The proliferative activities of H1299 cells in the three groups at 72 h were 0.80±0.01, 1.00±0.04 and 0.93±0.07 ( F=13.90, P=0.006) . The cell proliferation activity in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . Conclusion:SAMHD1 silencing induces PD-L1 expression in lung adenocarcinoma.

Detección de mutaciones del gen EGFR en ADN circulante por medio de biopsia líquida en pacientes con cáncer pulmonar de células no pequeñas: Revisión rápida / Detection of EGFR gene mutations in circulating DNA by liquid biopsy in patients with non-small cell lung cancer: Brief review

RESUMEN El cáncer pulmonar es un problema de salud pública debido a su alta morbimortalidad mundial y en el Perú. En el cáncer pulmonar de células no pequeñas (CPCNP) la detección de mutaciones del receptor del factor de crecimiento epidérmico (EGFR) ha sido útil para elección de la terapéutica de esta enfermedad. El presente artículo tiene como objetivo discutir la información actual y relevante sobre la biopsia liquida como técnica diagnóstica en detección de mutaciones del gen EGFR en pacientes con cáncer pulmonar de células no pequeñas. Las principales guías de cáncer y dos revisiones sistemáticas muestran evidencia a favor de la biopsia líquida en busca de mutaciones del gen EGFR, esto como una alternativa a la biopsia de tejido al inicio de diagnóstico y con una mayor aceptación de uso en el escenario clínico de pacientes con CPCNP con mutaciones sensibles de EGFR. Esta tecnología sanitaria puede ser útil en nuestro país, y proponemos su uso en dos escenarios clínicos.

ABSTRACT Lung cancer is a public health problem due to its high morbidity and mortality worldwide and in Peru. In non-small cell lung cancer, the detection of mutations of the epidermal growth factor receptor (EGFR) has been useful for the choice of therapeutics for this disease. In the present article we aim to discuss current and relevant information on the best diagnostic technique for EGFR in patients with non-small cell lung cancer. The main cancer guidelines and two systematic reviews showed evidence in favor of the diagnosis of EGFR gene mutations on liquid biopsy as an alternative to tissue biopsy at the beginning of diagnosis and with a greater acceptance use, in the clinical setting of NSCLC patients with sensitive EGFR mutations. This healthcare technology may be useful in our country, and we propose its use in two clinical scenarios.

Calvarial metastasis from adenocarcinoma of lung: An uncommon initial presentation diagnosed by cytology

Bone metastasis from lung primary is not uncommon and about one-third of bone metastases originate from lung. However, skull bone metastasis is uncommon from lung carcinoma. Metastasis to skull bone and scalp as an initial presentation of lung carcinoma is a very rare phenomenon. We have diagnosed a case of calvarial metastasis with scalp swelling as an initial presentation of adenocarcinoma of lung by fine-needle aspiration cytology in an aged female. Radiologically, it was suggested as tuberculous lesion but cytology gave the correct diagnosis. Here, we present a rare case of calvarial metastasis as a presentation of adenocarcinoma of lung in an elderly female

Invasive mucinous adenocarcinoma of lung: A case report and literature review / 吉林大学学报(医学版)

Objective: To investigate the clinical characteristics and diagnosis and treatment process of a patient with invasive mucinous adenocarcinoma (IMAs) of lung, and to improve the clinician's understanding of IMAs. Methods: The general materials, imaging manifestations and treatment plan of a patient with IMAs were collected, and the related literature review was conducted. Results: A 42-year-old female patient was admitted to hospital due to cough and expectoration, the CT examination results showed the bilateral lung patchy shadows∗ the patient was suspected of having pneumonia. After anti-infective treatment, the patient' s symptoms did not improve. The pathological findings of transbronchial lung biopsy (TBLB) and the examination of exfoliated cells of pleural fluid all showed inflammation, and the pathological result of percutaneous biopsy was IMAs. The result of gene detection was 2-point mutation in exon of KRAS. After chemotherapy with paclitaxel plus carboplatin combined with bevacizumab, the symptoms of the patients were improved significantly, and the changes of imaging manifestations were obvious. Conclusion: IMAs is a special pathological type of lung adenocarcinomas (ADCs) with various imaging manifestations and specific gene expression. The treatment principles are different from those of the other types of ADCs.

Circulating Tumor Cell Number Is Associated with Primary Tumor Volume in Patients with Lung Adenocarcinoma / 결핵

Hypoglycemia caused by co-secretion of insulin from lung tumor and cardia cancer: first case report

ABSTRACT CONTEXT: Non-islet-cell-tumor-induced hypoglycemia (NICTH) is caused on rare occasions by secretion of insulin from tumor cells that are reported to have a single tissue origin. CASE REPORT: A 67-year-old male patient had cardia adenocarcinoma and concomitant lung adenocarcinoma with extensive metastases and repeated episodes of intractable hypoglycemia. Immunohistochemical staining for insulin showed that lung adenocarcinoma stained positive and gastric cardia adenocarcinoma stained weakly positive. These results indicate that tumor cells of different tissue origins co-secreted insulin. CONCLUSIONS: This is the first report on intractable hypoglycemia due to co-secretion of insulin from two kinds of primary tumor cells in a single patient.

MRI differential diagnosis of early-stage lung invasive adenocarcinoma appearing as ground-glass nodule / 中国医学影像技术

Objective: To investigate value of MRI in differential diagnosis of early-stage invasive lung adenocarcinoma appearing as ground-glass nodule. Methods MRI findings in 34 patients with lung adenocarcinoma appearing as ground-glass nodule were analyzed retrospectively. According to the pathology, the patients were divided into non-invasive adenocarcinoma group (including atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma, n=15) and invasive adenocarcinoma group (n=19). The maximum diameter, T2WI signal intensity and ADC value were measured and compared between the 2 groups. ROC curves were used to evaluate the efficacy of differential diagnosis of invasive adenocarcinoma. Results The maximum diameter of lesions in non-invasive adenocarcinoma group was significantly less than that in invasive adenocarcinoma group ([9.91±2.63]mm vs [13.12±2.71]mm, P<0.01). T2WI signal intensity of lesions in non-invasive adenocarcinoma group was significantly lower than that in invasive adenocarcinoma group (92.97±8.33 vs 113.57±22.88, P<0.01). ADC value in non-invasive adenocarcinoma group was also significantly lower than that in invasive adenocarcinoma group ([0.98±0.22]×10-3 mm2/s vs [1.34±0.31]×10-3 mm2/s, P=0.01). ROC curve showed that the AUC of the maximum diameter was the highest, which value was 0.791, and the optimal cut-off value was 11.52 mm, with sensitivity of 73.72%, specificity of 73.33%. Conclusion The maximum diameter, T2WI signal intensity and ADC value are valuable for differential diagnosis of lung invasive adenocarcinoma from non-invasive lesions.

Caracterización de nódulos pulmonares resecados. Experiencia de manejo por un programa multidisciplinario / Features of excised pulmonary nodules in 100 patients

Background: Pulmonary nodules are common, and surgery is the only alternative that allows a diagnostic and therapeutic management in a single procedure. Aim: To report the epidemiological, radiological, surgical and pathological features of excised pulmonary nodules. Material and Methods: Review of medical records of patients in whom a pulmonary nodule was excised between 2014 and 2018. Those with incomplete data or without a pathological study were excluded from analysis. Results: We retrieved 108 records and 8 had to be excluded, therefore 100 patients aged 34 to 82 years (57% females) were analyzed. Sixty percent had a history of smoking. Mean nodule size was 16 mm and the solid type was the most common (65%). Forty five percent of nodules had irregular margins and 55% were in the superior lobes. All patients operated by video-assisted thoracoscopic surgery and 40% underwent a lobectomy. Malignant lesions were observed in 87% of biopsies and a pulmonary adenocarcinoma was found in pathology in 40%. Conclusions: A multidisciplinary approach of pulmonary nodules, using adapted international guidelines, accomplishes an appropriate management, decreasing unnecessary surgical interventions.

Research on intervention mechanism of Xiaoyan Decoction on apoptosis of lung adenocarcinoma A549 cells in tumor-burdened mice / 中草药

Objective: To analyze the elimination of Xiaoyan Decoction intervened survivin siRNA in lung adenocarcinoma A549 cells tumor-burdened mice tumor cell apoptosis. Methods: Human lung adenocarcinoma A549 entity nude mouse transplantation tumor model was studied as the research object. Xiaoyan Decoction medicated serum and siRNA cells after transfection group was injected within the tumor respectively by flow cytometry to observe apoptosis and cell cycle distribution in mice; Survivin protein expression was detected by immunocytochemistry method. Results: Transfection group's inhibition of the expression of survivin protein was obviously higher than that of Xiaoyan Decoction group, but significantly lower than Xiaoyan Decoction and siRNA group. Transfection group and Xiaoyan Decoction both could induce cell apoptosis, and induction effect of transfection group was stronger than Xiaoyan Decoction group, Xiaoyan Decoction combined with transfection group could ernhance the induction of cell apoptosis. Conclusion: Xiaoyan Decoction combined with Survivin apoptosis induced by siRNA can synergy to enhance its role.