RESUMO
The outcome of colon adenocarcinoma (COAD) patients remains dismal, and lactate metabolism has been characterized to promote tumor development and immune evasion. Based on the above background, it is worthwhile to explore novel prognostic and therapeutic biomarkers for COAD patients from the aspect of lactate metabolism. Above all, 228 available lactate-metabolism-related genes (LMRGs) were acquired, and the landscape of copy number variation and the expression difference of mRNA levels between colon normal and tumor samples were investigated among these LMRGs. Importantly, eight overall survival (OS)-involved LMRGs were then distinguished by means of univariate Cox regression analysis in both GSE40967 and TCGA-COAD data sets. Subsequently, prognostic risk scores were established, integrating seven OS-related LMRGs by LASSO Cox regression analysis in the GSE40967 set, and then verified in the TCGA-COAD cohort. From the comprehensive analyses, COAD patients with high risk had comparatively more inferior survival probability in all populations of the study, and they tended to have more severe clinicopathological features with the risk score increasing. Moreover, by integrating age, AJCC T and pathological stage, and risk score, we constructed a prognostic nomogram that demonstrated great prediction effectiveness for OS of COAD patients. Furthermore, the potential effect of various risk score on tumor immune was assessed from enrichment of immune-related pathways, tumor-infiltrating immune cells, and expression levels of immune checkpoints separately. We could draw a conclusion that COAD patients with higher lactate-metabolism-related risk scores may acquire an immunosuppressive tumor microenvironment, which subsequently led to immune escapes and poor prognoses. Conclusively, all findings in the present study illustrate a great prognostic value of the lactate-metabolism-related risk signature, providing more in-depth insights into the indispensable function of lactate metabolism in prognosis and tumor immunity of COAD.
RESUMO
AIMS: Associations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)/mannose-binding lectin (MBL)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/phospholipase C ε-1 (PLCE1) and gastric cancer (GC) were already reported by many studies, yet the conclusions of these studies were somehow controversial. The aim of this meta-analysis was to better clarify associations between polymorphisms in CTLA-4/MBL/IL-4/IL-6/PLCE1 and GC by combing the results of all relevant studies. METHODS: Eligible studies were searched from PubMed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies. RESULTS: Forty-three studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs5742909 (dominant comparison: OR: 1.58, 95 % CI: 1.01 to 2.48; allele comparison: OR: 1.69, 95 % CI: 1.12 to 2.56) and PLCE1 rs2274223 (dominant comparison: OR: 0.84, 95 % CI: 0.72 to 0.98; recessive comparison: OR: 1.23, 95 % CI: 1.08 to 1.40; over-dominant comparison: OR: 1.16, 95 % CI: 1.00 to 1.34; allele comparison: OR 0.88, 95 % CI 0.78 to 0.99) polymorphisms were significantly associated with GC in the general population. We also obtained similar significant associations with GC for rs5742909 and rs2274223 polymorphisms in East Asians. Nevertheless, no positive results were observed for the other eight investigated polymorphisms. CONCLUSION: Collectively, this meta-analysis demonstrated that CTLA-4 rs5742909 and PLCE1 rs2274223 polymorphisms may confer susceptibility to GC, especially for East Asians.
