Association between baseline C­reactive protein level and survival outcomes for cancer patients treated with immunotherapy: A meta­analysis.

The prognostic impact of baseline C-reactive protein (CRP) in patients with cancer receiving immune checkpoint inhibitors (ICIs) is unclear. The present meta-analysis aimed to review the prognostic value of baseline C-reactive protein (CRP) levels for patients with cancer receiving immunotherapy. Electronic databases, including PubMed, EMbase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, WanFang, Chinese Literature Biomedical Database and Weipu Database, were used to identify cohort studies on the relationship between the baseline CRP levels and ICI survival outcomes from inception to November 2020. Literature screening, data extraction and quality evaluation of studies were independently performed by two reviewers. Subsequently, a meta-analysis was performed using STATA 14.0. A total of 13 cohort studies comprising 2,387 patients with cancer were included in the present meta-analysis. The results indicated that high baseline CRP levels (serum CRP measured within 2 weeks before ICI treatment) were associated with low overall survival (OS) and progression-free survival (PFS) rate among patients treated with ICIs. The subgroup analysis based on cancer type showed that high baseline CRP levels were associated with poor survival outcomes of multiple types of cancer, such as non-small cell lung cancer (6/13; 46.2%), melanoma (2/13; 15.4%), renal cell (3/13; 23.0%) and urothelial carcinoma (2/13; 15.4%). Similar results were observed in subgroup analysis based on the CRP cut-off value of 10 mg/l. In addition, a higher mortality risk was reported in patients with cancer and CRP ≥10 mg/l (hazard ratio, 2.76; 95% CI, 1.70-4.48; P<0.001). Compared with patients with low baseline CRP levels, increased baseline CRP levels were associated with low OS and PFS rate in patients with cancer receiving ICIs. Furthermore, CRP ≥10 mg/l indicated a worse prognosis. Therefore, baseline CRP levels may serve as a marker for the prognosis of patients with certain types of solid tumor treated with ICIs. Due to the limited quality and quantity of included studies, more prospective well-designed studies are required to verify the present findings.

A patient with advanced lung squamous cell carcinoma who failed to benefit from albumin bound paclitaxel plus pembrolizumab achieved partial response with second-line treatment of docetaxel plus pembrolizumab: a case report.

BACKGROUND: Lung cancer, including squamous cell lung cancer and non-squamous non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths. At present, for squamous cell lung cancer patients who have progressed on first-line chemotherapy plus immunotherapy, immunotherapy applied across the line is still inconclusive. Therefore, treatment for such patients is often challenging. CASE DESCRIPTION: We present a 53-year-old male patient who found lung mass in August 2021, without symptoms of cough, expectoration or hemoptysis. Through imaging examinations, we found he got tumor of upper lobe in right lung, with left lung metastasis and lymph node metastasis in the right hilar. Bronchoscopy biopsy showed poorly differentiated squamous cell carcinoma of the right lung. Gene screening showed TP53 mutation. The patient was diagnosed as stage IVA (cT2aN1M1b) squamous cell carcinoma. He was administered four cycles of first-line albumin-binding paclitaxel + carboplatin combined with pembrolizumab. Reexamination of chest CT (2022-01-10) showed both right lung lesions and right hilar lymph nodes were progressed after progression free survival (PFS) of four months. After received two cycles of second-line therapy (docetaxel + carboplatin combined with pembrolizumab), the lung lesions shrunk significantly with efficacy of partial response (PR). As of 2022-05-18, he received a total of five cycles of second-line regimen. During this period, the disease was stable. No adverse events related to chemotherapy or immunotherapy were observed during the treatment. This is the first report of a successful case with an advanced lung squamous cell carcinoma patient who achieved disease remission after first-line progressed disease and second-line immunotherapy combined with chemotherapy. This case suggests that for such patients who fail to response to the first-line albumin-bound paclitaxel combined with immunotherapy, may get favorable response to docetaxel combined with immunotherapy. We need further investigations to validate that. CONCLUSIONS: This case suggested advanced lung squamous cell carcinoma patients who have failed to respond to first-line albumin paclitaxel combined with immunotherapy may still benefit from second-line docetaxel combined with immunotherapy. In addition, presentation of the TP53 mutation may be useful in predicting patients who may be responsive to docetaxel plus immunotherapy.

Comparative clinical analysis of fever in tumor patients, normal patients, and those infected with new coronavirus pneumonia.

BACKGROUND: Under the current epidemic of the coronavirus disease of 2019 (COVID-19), there is a need to distinguish the differences between the laboratory examinations of COVID-19-infected patients, tumor patients with fever, and those with normal fever patients. We aimed to investigate the temperature of tumor patients with different tumor burdens, stages, and cancer types. METHODS: We recruited 3 groups of patients to this study: fever patients with malignant tumors, ordinary fever patients, and confirmed cases of COVID-19, with 31, 55, and 28 cases in each group, respectively. RESULTS: The levels of leukocytes and neutrophils were the highest among non-tumor patients, and the count of COVID-19 was the lowest, with a P value of 0.000. Among the leukocytosis group, non-tumor patients had the highest proportion (43.6%), while that of COVID-19 was only 3.6% (P=0.000). Similarly, there were significant differences in the grading of neutrophils, where most of the infected patients were in the normal group and the P value was 0.000. The lymphocyte count of the tumor group was significantly reduced, with an average of (0.97±0.66) ×109/L (P=0.004). In the lymphocyte grades, most of the infected patients were the normal group (71.4%), while tumor patients in the lymphocytopenia group accounted for 63.1% (P=0.006). There were also significant differences in the neutrophil to lymphocyte ratio (NLR) (P=0.006). There was a significant difference in temperature between different tumor burden groups (P=0.014). CONCLUSIONS: The normal fever group had the highest count of leukocyte and neutrophils, whereas the infected group had the lowest relative count. The NLR was the lowest in the infected group. The NLR was higher in the bigger tumor load group.

Novel mutation signatures in the prognosis of EGFR-TKIs targeted therapy for non-small cell lung cancer patients based on the 1000-gene panel sequencing.

The application of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) may be affected by somatic mutations. The purpose of this study was to explore the effect of mutations on the prognosis and tumor markers of NSCLC patients treated with EGFR-TKIs. 21 NSCLC patients treated with EGFR-TKIs were selected, and the targeted sequencing of the tumor tissues or whole blood samples with the 1000-gene panel was conducted to screen mutations. Afterward, functional enrichment analysis was performed based on mutant genes. Subsequently, the correlation between mutations and clinical indicators, prognosis, and tumor markers were analyzed. Finally, the prognosis after taking osimertinib was compared between NSCLC patients with EGFR p.T790M positive and negative mutations, and the EGFR p.T790M concomitant and uncommon mutations were screened. A total of 485 mutations in 251 genes were identified, in which MTOR, AXIN2, AR, EGFR, NOTCH1, and HRAS mutations were significantly correlated with PFS and/or tumor markers. There was no significant difference in PFS, therapeutic effect, and prognosis between EGFR p.T790M positive and negative patients who received osimertinib treatment. Besides, we also found 80 concomitant mutations and 54 uncommon mutations of EGFR p.T790M. AR, HRAS, EGFR, AXIN2, NOTCH1, and MTOR might be key genes to the prognosis of NSCLC treated with EGFR-TKIs. Osimertinib has certain efficacy in EGFR p.T790M negative NSCLC patients.

Diagnostic Value of Imaging Combined With Tumor Markers in Early Detection of Lung Cancer.

Objective: The objective of this research is to explore the diagnostic value of imaging plus tumor markers in the early detection of lung cancer. Methods: Sixty patients with lung cancer treated in our hospital from January 2018 to January 2019 were selected as group A. They were matched with 60 patients with benign lung disease as group B and 60 healthy subjects examined in our hospital as group C. The carcino-embryonic antigen (CEA), CYFRA21-1, and neuron-specific enolase (NSE) were assessed, and the diagnostic value of tumor markers plus imaging in lung cancer diagnosis was explored. Results: The CEA, CYFRA21-1, and NSE in group A were evidently superior to those in groups B and C, and those in group B were superior to those in group C (all P < 0.001). CEA had the highest sensitivity (56.7%), and NSE had the highest specificity (93.3%). The tumor markers plus imaging had the highest sensitivity for different types of lung cancer, and the sensitivity to early lung cancer (90%) was superior to other diagnostic methods (P < 0.05). Conclusion: The tumor markers plus imaging is of great significance in early lung cancer diagnosis and provides a reference for judging the pathological classification.

Genomic alteration profiles of lung cancer and their relationship to clinical features and prognosis value using individualized genetic testing.

BACKGROUND: This study aimed to use a panel targeting 197 genes and 38 fusions to observe the features of gene variations in lung cancer patients, as well as their prognostic values. METHODS: Patients admitted to our hospital between 2016 and 2017 were enrolled. All patients received OseqTM-Drug genetic testing using peripheral venous blood, followed by 1-2 years of observation. RESULTS: For all included patients, 32 genes were observed with mutations. EGFR exhibited the highest mutation rate (46.5%), followed by TP53. The majority of patients carried only one mutant gene. Interestingly, 18 (41.8%) patients showed no mutations, and some cases carried mutations in six genes simultaneously. There was no statistical relationship between mutations and demographic influence. Pathological subtypes were associated with mutations including FLI1, IGF1R, and NOTCH1. A significant correlation was observed between mutant genes and stage at diagnosis, however this requires further confirmation as there was only one case in these mutations: AKT2, AR, STK11, VEGFA, HDAC6, and ASPSCR. For the 33 patients with lymph node metastases at the time of diagnosis, no correlation with any gene mutant was found. Finally, no associations between the survival or prognosis indices (1-year survival, 1-year progression, progression free survival (PFS), and overall survival (OS)) were observed with gene mutations. CONCLUSIONS: Together, individualized genetic testing is a feasible and minimally invasive approach in cancer genetic analysis. However, gene mutation detection has a limited efficacy in the prediction of prognosis.

CircRNA_0000429 Regulates Development of NSCLC by Acting as a Sponge of miR-1197 to Control MADD.

BACKGROUND: Non-small-cell lung carcinoma (NSCLC) is the most common type of lung cancer. Circular RNA_0000429 (circ_0000429) is an identified circular RNA (circRNA) that is correlated with cancer progression. However, the role of circ_0000429 in NSCLC remains unknown. In the present study, we aimed to investigate the function of circ_0000429 in NSCLC and the underlying mechanism. METHODS: The expression patterns of circ_0000429 were determined using qRT-PCR in NSCLC samples and cell lines. The subcellular distribution of circ_0000429 in NSCLC cells was analyzed by fluorescence in situ hybridization (FISH). Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the transwell assay. We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNA-mRNA interactions. RESULTS: Our results showed that circ_0000429 expressions were significantly upregulated in NSCLC tissues and cell lines. Knockdown of circ_0000429 significantly inhibited the cell proliferation, migration, and invasion of NSCLC cells in vitro. Furthermore, we demonstrated that circ_0000429 acted as a sponge to absorb microRNA-1197 (miR-1197) and promoted MADD expression. CONCLUSION: Collectively, our results demonstrated that circ_0000429 exhibited a carcinogenic role by sponging miR-1197 and regulating CMADD expression in NSCLC. These findings provided evidence for understanding the role of circ_0000429 in NSCLC tumorigenesis.

LncRNA PTCSC3 Inhibits Tumor Growth and Cancer Cell Stemness in Gastric Cancer by Interacting with lncRNA Linc-pint.

BACKGROUND: The tumor suppressor role of lncRNA PTCSC3 has been reported in papillary thyroid carcinoma, our study aimed to investigate its involvement in gastric cancer. METHODS: Tumor tissues and adjacent healthy tissues were collected from gastric cancer patients. Expression of PTCSC3 and lncRNA Linc-pint in these tissues was analyzed by RT-qPCR. The interaction between PTCSC3 and Linc-pint was analyzed by overexpression experiments. Cell proliferation and stemness were analyzed by CCK-8 assay and cell stemness assay, respectively. RESULTS: PTCSC3 and lncRNA Linc-pint were both downregulated in tumor tissues than in adjacent healthy tissues of gastric cancer patients. Low levels of PTCSC3 and Linc-pint were closely correlated with poor survival. PTCSC3 and Linc-pint overexpression inhibited tumor growth and cancer cell stemness, while Linc-pint knockdown played an opposite role an attenuated the effects of PTCSC3 overexpression. Expression levels of PTCSC3 and Linc-pint were significantly correlated in tumor tissues but not in adjacent healthy tissues. Overexpression of PTCSC3 and Linc-pint upregulated the expression of each other. CONCLUSION: PTCSC3 inhibits tumor growth and cancer cell stemness in gastric cancer by interacting with lncRNA Linc-pint.

Linc­pint overexpression inhibits the growth of gastric tumors by downregulating HIF­1α.

Long intergenic non­protein coding RNA, p53 induced transcript (Linc­pint) has been reported to be downregulated in various cancer cell lines; however, its expression profile and role in gastric cancer remains unknown. The present study aimed to investigate the involvement of Linc­pint in gastric cancer. Through quantitative polymerase chain reaction, western blotting and viability assays, it was observed that Linc­pint expression was significantly downregulated in gastric biopsies from patients with gastric cancer, compared with healthy controls. Conversely, the expression of hypoxia­inducible factor­1α (HIF­1α) mRNA was significantly upregulated in patients with gastric cancer compared with in healthy controls. Using a variety of statistical inference tests, including receiver operating characteristic curve and correlation analyses, it was determined that the expression levels of Linc­pint and HIF­1α exhibited a significantly negative correlation in patients with gastric cancer but not in healthy controls. Linc­pint expression was significantly and inversely associated with tumor size but not tumor metastasis. Linc­pint overexpression inhibited the proliferation of gastric cancer cells, whereas treatment with exogenous HIF­1α promoted proliferation. Linc­pint overexpression downregulated the expression of HIF­1α, whereas exogenous HIF­1α did not significantly alter Linc­pint expression. Furthermore, treatment with exogenous HIF­1α suppressed the inhibitory effects of Linc­pint overexpression on the proliferation of gastric cancer cells. In conclusion, overexpression of Linc­pint may inhibit the growth of gastric tumors via downregulation of HIF­1α.

Novel loss-of-function mutation in BRCA2 gene identified in a Chinese female with a family history of ovarian cancer: A case report.

Inherited loss-of-function mutations in the tumor suppressor BRCA2 gene are associated with a high risk of ovarian cancer in the Chinese population. The current case report discusses a novel heterozygous insertion in BRCA2 gene, c.3195_3196insA, in a 54-year-old Chinese female with hereditary ovarian cancer. This frameshift mutation generates a premature stop codon at amino acid 1,076, which leads to a truncated BRCA2 protein instead of a wild-type BRCA2 protein with 3,418 amino acids. According to the Breast Cancer Information Core database, this mutation has not been previously reported. However, germline mutations of BRCA2 are a more prevalent cause of ovarian cancer in Chinese females compared with females in Western populations. The present study expands the mutational spectra of BRCA2 that is associated with ovarian cancer.

[Research Progress of KRAS Mutation in Non-small Cell Lung Cancer].

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all patients with lung cancer, the majority of patients with lung cancer at the time of diagnosis is in the advanced stage. The development of target therapy based on has changed the mode of treatment in patients with advanced NSCLC. In NSCLC, epidermal growth factor receptor mutation (EGFR) fusion with echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) has been shown to be a powerful biomarker. It is well known that KRAS is also NSCLC one of the most common mutations in oncogenes, although more than 20 years ago KRAS mutation was found in NSCLC. At present, although there are many drugs used to treat NSCLC patients with KRAS mutation, there is no selective or specific inhibitor for the direct elimination of KRAS activity. NSCLC patients with KRAS mutation have poor responsiveness to most systemic therapy. However, individualized therapy for activated signaling pathways with targeted drugs has a good effect on the prognosis of NSCLC patients with KRAS mutation. In addition, the prognostic and predictive role of KRAS mutation in NSCLC remains unclear. In this review, we focus on the research progress of NSCLC with KRAS mutation, including molecular biology, clinicopathological features, prognosis and prediction of KRAS mutation, which will help to improve the understanding of NSCLC in KRAS mutation.
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[Analysis of the factors associated with abnormal coagulation and prognosis
 in patients with non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: The activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are associated with high risk of invasion, metastases, and negative final outcomes. Non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85% of all lung malignancies. This study aims to investigate the prognostic value of blood coagulation tests for NSCLC and provide a reference to patients on the prevention and treatment of thrombophilia. METHODS: Data were collected from 604 cases of hospitalized patients with histologically confirmed NSCLC from January 2009 to December 2012 at the Fourth Hospital of Hebei Medical University. Data included the related indexes of coagulation function in patients before treatment [(i.e., prothrombin time (PT), prothrombin time activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib), D-dimer, and platelet count)], as well as sex, age, pathological type, TNM stage, and lymph node status. Fifty control subjects without cancer were included in the analysis. Statistical analysis was conducted by using SPSS 13.0 software. RESULTS: The plasma level of all coagulation tests including D-dimer, Fib, PT, APTT, INR, and platelet counts revealed statistically significant differences between the patient and control group (P<0.001 for all variables; P=0.001,5 and P=0.004,5 for Fib and platelet counts, respectively). The squamous subtype exhibited high plasma Fib levels (P<0.001) compared with adenocarcinoma cell lung cancer patients. Fib and PLT levels increased (P<0.001 and P=0.014, respectively), and aPTT decreased (P<0.001) in patients at stages III and IV compared with those in patients at stages I and II. aPTT decreased significantly (P<0.001), and Fib and D-dimer levels increased (P<0.001 and P=0.048, respectively) in N1-3 patients with NSCLC compared with those of N0 patients. Prolonged PT and INR, high plasma Fib levels, and low PTA levels had statistically significant adverse effects on survival (P=0.032, P=0.001, P<0.001, and P=0.005, respectively). Multivariate analyses revealed that only increased INR was associated with a decreased survival rate in the related indexes of coagulation function (P=0.017). CONCLUSIONS: Patients who have lung adenocarcinoma and/or lymph node metastasis at advanced stages of NSCLC are prone to thrombophilia. Prolonged PT and INR was associated with poor prognosis, and elevated INR was independently associated with a decreased survival rate. PT and INR are promising prognostic markers of NSCLC.

[Advances on mechanisms of coagulation with non-small cell lung cancer].

Recently, researchers have been increasingly finding coagulation disorders are commonly the first sign of malignancy. It has now been established that cancer development leads to an increased risk of thrombosis, and conversely, excessive activation of blood coagulation profoundly influences cancer progression. In patients with lung cancer, a sustained stimulation of blood coagulation takes place. Cancer cells trigger coagulation through expression of tissue factor, and affect coagulation through expression of thrombin, release of microparticles that augment coagulation and so on. Coagulation also facilitates tumour progression through release of platelet granule contents, inhibition of natural killer cells and recruitment of macrophages. Non-small cell lung cancer (NSCLC) accounts for about 80%-85% of all lung malignancies. In the present review, we summarized the newly updated data about the physiopathological mechanisms of various components of the clotting system in different stages of carcinogenesis in NSCLC.

[Clinical observation on treatment of cancerous hydrothorax by aiyishu injection].

OBJECTIVE: To investigate the therapeutic effects of Aiyishu Injection (AYSI) on cancerous hydrothorax, quality of life (QOF), and cellular immune function of patients. METHODS: Sixty late-stage cancer patients accompanied hydrothorax were randomly divided into the experimental group (EG) and the control group (CG), with thirty patients in each group. After thoracenteses being carried out in all patients for draining off hydropsy, to the patients in EG, AYSI was medicated, 50 ml by intrathoracic and another 50 ml by intravenous injection; while to the patients in CG chemotherapeutic agent or interleukin-2 (IL-2) was given. The same treatment, thoracentesis and medication, was repeated 3 days later. After 4 weeks, the volume of pleural effusion was measured with B-mode ultrasound to evaluate the therapeutic effects of AYSI. QOF, body weight and T-lymphocyte subsets were compared between the two groups before and after treatment. RESULTS: The clinical efficacy was significantly higher in EG than that in CG (P < 0.01). Besides, QOF was significantly improved (P < 0.05) and levels of CD3+ , CD4+ , CD4+ /CD8+ in peripheral blood increased in EG after treatment, which were significantly different to those in CG (P < 0.01, P < 0.05). CONCLUSION: AYSI has definite therapeutic effects on cancerous hydrothorax, it could improve QOF and cellular immune function in patients with cancer.