Polymorphisms of matrix metalloproteinases affect the susceptibility of esophageal cancer: Evidence from 20412 subjects, systematic review and updated meta-analysis.

BACKGROUND: The results of how matrix metalloproteinases (MMPs) polymorphisms affect esophageal cancer (EC) risk are not consistent, especially for MMP1,2,7 and 9. A meta-analysis focused on the impact of MMPs to digestive cancers, but not a precise analysis to EC, therefore, we designed the current study to make a clear understanding of the association between MMPs polymorphisms and EC. METHODS: Up to March 2020, we searched several databases to find case-control cohorts concerned about the risk of MMPs polymorphisms to EC risk. Odds ratios with 95% confidence intervals under five genetic models to generate the risk predicted value. The Q test and I2 statistics are used to estimate heterogeneity. Sensitivity analysis, Egger test, and Begg's funnel plot were employed to assess the results. In-silico analysis was performed to study the association between the polymorphism and mRNA expression. RESULTS: 19 case-control studies were enrolled, including 8371 EC patients and 12041 health controls. We observed the increased risk in BA vs. AA and BB + BA vs. AA models of MMP1-rs1799750 polymorphism. The protective effectiveness of EC was found in the MMP2 rs243865 polymorphism in B vs. A, BA vs. AA, and BB + BA vs. AA models. Meanwhile, the risk effect was also observed in the MMP7 rs11568818 polymorphism in most genetic models. In the furthermore bioinformatics analysis, we found that MMP1, MMP3, MMP7, MMP9, MMP12, MMP13 all increased in the tumor tissues, and the genetic alteration in the polymorphisms could impact the mRNA expression of the above MMPs. CONCLUSION: MMP1 rs1799705 and MMP7 rs1156818 polymorphisms will take part in the tumorigenesis of EC, while MMP2 rs243865 acts as a protective role to decrease the risk of EC.

A Novel Tool for the Risk Assessment and Personalized Chemo-/Immunotherapy Response Prediction of Adenocarcinoma and Squamous Cell Carcinoma Lung Cancer.

BACKGROUND: The prevalence and cancer-specific death rate of lung cancer (LC) have risen in recent decades. A universally applicable prognostic signature for both adenocarcinoma LC (LUAD) and squamous cell carcinoma LC (LUSC) is still lacking. METHODS: A total of 453 patients from The Cancer Genome Atlas (TCGA)-LUAD cohort and 452 patients from TCGA-LUSC cohort were enrolled, and a prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression analysis based on the consensus prognostic genes in both cohorts. The newly defined pan-lung cancer risk count (PLCRC) of each patient was calculated via the summation formula. RESULTS: A total of 23 genes were selected for the calculation of the PLCRC. The PLCRC showed a moderate prognostic value in the entire (p < 0.001, HR: 2.75, AUC: 0.643), LUAD (p < 0.001, HR: 2.51, AUC: 0.636) and LUSC (p < 0.001, HR: 2.89, AUC: 0.656) cohorts. The PLCRC was an independent prognostic factor after adjusting the clinical features. The PLCRC was also effective in nine external validation cohorts and in patients with different clinical features. Activation of extracellular matrix pathways and infiltration of immunocytes promoted the tumorigenesis and development of both LUAD and LUSC. We generated a universally applicable prognostic signature, the PLCRC, which could dichotomize patients with significantly different clinical outcomes and guide the clinical treatment of LC patients. Chemotherapy is more suitable for patients with a low PLCRC, while anti-cytotoxic T-lymphocyte-associated protein 4 immunotherapy is more suitable for patients with a high PLCRC. CONCLUSION: We established and validated a newly defined prognostic signature, the PLCRC, for both LUAD and LUSC patients and provided clinical strategies for patients from different risk subgroups.

[The Relationship of Clinicopathology of p16 in Non-small Cell Lung Cancer and 5-nitrogen impurity-2'-deoxycytidine-nitrogen Impurity on the Influence of p16 Expression in Lung Cancer A549 Cells].

OBJECTIVE: To investigate the relationship between expression of tumor suppressor gene p16 in non-small cell lung cancer (NSCLC) tissues and clinicopathological parameters,to further study on DNA methyltransferase inhibitors 5-nitrogen impurity-2'-deoxycytidine (5-Aza-CdR) in human lung cancer cell line A549 in regulating the expression of p16. METHODS: The expression of p16 protein in 76 cases of NSCLC tissues and normal tissue adjacent to carcinoma were detect by immunohistochemical SP method and the differences of p16 protein expression were analyzed. p16 gene promoter region of DNA methylation status were detect by MSP method in 5-Aza-CdR processing A549 cells,the expression of p16 in A549 lung cancer cell and effect of 5-Aza-CdR were detect by Western blot method. RESULTS: 32 cases (42.11%) of p16 protein expression was positive,significantly lower than that of the normal tissue adjacent to carcinoma (positive expression in 59 cases,77.63%) in 76 cases of NSCLC tissues; There were statistically significant differences (P<0.05) in the positive expression rates of p16 in NSCLC tissues with different pathological tissue grading,tumor differentiation degree,clinical TNM stage and lymph node metastasis. In A549 cells,p16 protein expression and non-methylated products were both in low expression states. After treated with 5-Aza-CdR,the expression of p16 protein and its non-methylated products were up-regulated,with the increase of 5-Aza-CdR concentration. CONCLUSION: The low expression of p16 in NSCLC tissues with squamous cell carcinomas,low differentiation,lymph node metastasis and phase Ⅲ-Ⅳ,which may prompt the deactivation and cause further progression of NSCLC,5-Aza-CdR could induce the expression of p16 protein and non-methylated products in A549 cells.