The Prognostic Significance of Lymph Node Ratio for Esophageal Cancer: A Meta-Analysis.

INTRODUCTION: This meta-analysis aimed to investigate the prognostic significance of positive lymph node ratio (LNR) in patients with esophageal cancer. MATERIALS AND METHODS: The meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a systematic search of relevant literature published until April 2022 in PubMed, EMBASE, and the Cochrane Library. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), with corresponding hazard ratios (HR) and 95% confidence intervals (CI). The included studies were subgrouped based on age, study area, adjuvant therapy, sensitivity analysis, and assessment of publication bias. We analyzed and discussed the results. RESULTS: We included 21 studies with 29 cohorts and 11,849 patients. The Newcastle-Ottawa Scale scores of the included studies were no less than six, indicating high research quality. The combined results of HR and 95% CI showed that patients with esophageal cancer with a lower LNR had better OS (HR, 2.58; 95% CI, 2.15-3.11; P < 0.001) and DFS (HR, 3.07; 95% CI, 1.85-5.10; P < 0.001). The subgroup analysis suggested that geographic region, age, and adjuvant therapy affected OS. When any cohort was excluded, no significant changes were observed in the pooled HR of the OS group, indicating reliable and robust results. Egger's and Begg's tests showed no potential publication bias in the studies that used OS as an outcome measurement index, indicating reliable results. Sensitivity analyses and assessments of publication bias (<10) were not performed because of an insufficient number of DFS studies. CONCLUSION: Patients with a lower positive LNR had a higher survival rate, suggesting that positive LNR may be a promising predictor of EC prognosis in esophageal cancer. After radical resection of esophageal cancer, the ratio of the number of dissected lymph nodes to the number of positive lymph nodes in patients with esophageal cancer should be considered to accurately evaluate the prognosis.

LAGE3 promotes cell metastasis and stemness in non-small cell lung cancer companied with AKT/PI3K signaling pathway activation.

BACKGROUND: Non-small cell lung cancer (NSCLC) is reported to have high mortality and morbidity rate worldwide. It is highly susceptible to metastasis. Previous reports have shown the L antigen family member 3 (LAGE3) expression in many cancers and has a carcinogenic role. However, the molecular mechanism of LAGE3 in NSCLC needs to be further explored. METHODS: LAGE3 expression profile of NSCLC patients and normal samples in the TCGA cohort was utilized for visualization. Expression pattern of LAGE3 in cell lines of NSCLCs were determined through qRT-PCR. Further, transfection experiments was conducted to measure the LAGE3's effect on the migration, proliferation, invasion, and stemness in NSCLC cell lines (A549 and H1975) by the assays of CCK-8, colony formation, EdU, transwell, and flow cytometry. The in vivo xenograft tumor growth in the nude mouse was conducted to confirm LAGE3 effect on NSCLC tumor growth. Furthermore, western blotting was applied to determine the levels of core proteins including AKT/PI3K signaling pathway and stemness proteins of Nanog, OCT4 and SOX2. RESULTS: The TCGA based computational analysis showed that LAGE3 mRNA level in NSCLC was inter-related to worse overall survival. The up-regulated level of LAGE3 in NSCLC cell lines indicated its possibility as a future diagnostic and prognostic biomarker. Functional assays showed that cell migration, proliferation, invasion, sphere formation, and stemness-related protein (Nanog, SOX2, and OCT4) levels were significantly repressed by the knockdown of LAGE3. Subsequently, inhibition of LAGE3 in nude mice (in vivo) demonstrated its ability to reduce the tumor growth of NSCLC. The study also showed that LAGE3 knockdown suppressed cell progression by inactivating the signaling pathway of AKT/PI3K. CONCLUSIONS: LAGE3 could promote NSCLC development by activating the AKT/PI3K signaling pathway, thereby accelerating metastasis and cell stemness.

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.