RESUMO
Neurotransmitters are reported to be involved in tumor initiation and progression. This study aimed to elucidate the prognostic value of γ-aminobutyric acid type A receptor δ subunit (GABRD) in colon adenocarcinoma (COAD) using the data from The Cancer Genome Atlas (TCGA) database. The GABRD mRNA expression levels in the COAD and normal tissues were compared using the Wilcoxon rank-sum test. The correlation between clinicopathologic characteristics and GABRD expression was analyzed by Wilcoxon rank-sum test or Kruskal-Wallis test and logistic regression. The prognostic value of GABRD mRNA expression in patients with COAD was determined using the Kaplan-Meier curve and Cox regression analysis. Finally, the molecular mechanisms of GABRD in COAD were predicted by gene set enrichment analysis (GSEA). The COAD tissues exhibited higher GABRD mRNA expression levels than the normal tissues. The logistic regression analysis revealed that GABRD mRNA expression was correlated with TNM stage, N stage, M stage, and microsatellite instability (MSI) status. The Kaplan-Meier survival curve and log-rank test revealed that patients with COAD exhibiting high GABRD mRNA expression were associated with poor overall survival (OS). The multivariate analysis indicated that increased GABRD mRNA expression was an independent prognostic factor and was correlated with a poor OS. The GSEA revealed that GABRD was involved in signaling pathways, including cell adhesion molecules, gap junction, melanogenesis, and mTOR signaling pathway, as well as the signaling pathways associated with basal cell carcinoma or bladder cancer development. In summary, enhanced GABRD mRNA expression may be a potential independent prognostic biomarker for COAD.
RESUMO
BACKGROUND: Microsatellite stable (MSS) BRAF p.V600E mutation colorectal cancer (BRAF-CRC) has a poor prognosis, whereas microsatellite instability (MSI) in BRAF-CRC is associated with a favorable prognosis. Although usually considered a single clinical entity, the MSI BRAF-CRC subtype shows some distinct characteristics in comparison with the MSS BRAF-CRC subtype. METHODS: We conducted a meta-analysis to investigate the influence of clinicopathological features on MSI status in BRAF-CRC. We searched publications up to March 2019 from PubMed, Embase, and the Cochrane Library. The effect of MSI status on outcome parameters was assessed using odds ratios (ORs) with 95% confidence intervals (CIs) and fixed- or random-effects models according to the heterogeneity. RESULTS: After reviewing 2839 reports, 16 eligible studies including 1381 patients with BRAF-CRC met the criteria. The MSI BRAF-CRC subtype was associated with older age, female sex (OR = 1.70; 95% CI = 1.35-2.14; P < 0.00001), proximal tumor location (OR = 5.10; 95% CI = 3.70-7.03; P < 0.00001), early TNM stage (OR = 5.28; 95% CI = 3.93-7.09; P < 0.00001), and poor differentiation (OR = 2.29; 95% CI = 1.60-3.28; P < 0.00001). CONCLUSIONS: MSI was significantly correlated with distinct favorable clinicopathological characteristics in BRAF-CRC. These results suggest that MSI status should be considered as a stratification factor for better management of the BRAF-CRC.
