目的 探讨胃癌组织中Ⅵ型胶原蛋白α2链(collagen type Ⅵ α2 chain ,COL6A2)的表达情况、临床意义及可能的作用机制。方法 采用免疫组化法检测62例胃癌组织及配对的癌旁组织中COL6A2蛋白的表达情况,统计分析COL6A2蛋白与患者临床病理特征之间的相关性。利用Kaplan-Meier法绘制生存曲线图,并用Kaplan-Meier Plotter 在线数据集进行生存验证。下载癌症基因组图谱(the cancer genome atlas,TCGA)数据库中的胃癌表达数据,分析COL6A2与上皮间质转化(epithelial mesenchymal transition,EMT)相关基因表达的相关性。并运用基因探针富集分析(gene set enrichment analysis,GSEA)探究COL6A2在胃癌中的可能作用机制。结果 COL6A2在胃癌组织中的阳性表达率显著高于配对癌旁组织(43.5% vs. 25.8%,P=0.038),与淋巴结转移,远处转移及TNM分期显著相关,差异有统计学意义(P<0.05)。生存分析及Kaplan-Meier Plotter均提示高表达COL6A2的胃癌患者生存时间较短。COL6A2是影响胃癌患者的独立预后因素(HR=2.339,95%CI: 1.150~4.757,P=0.019)。相关性分析发现,COL6A2与EMT相关蛋白的表达密切相关;GSEA结果显示,高表达COL6A2样本主要富集的基因集中包括TGF-beta信号通路及MAPK信号通路等经典肿瘤信号通路。结论 COL6A2在胃癌组织中呈显著高表达,且与预后不良有关,可作为判断胃癌患者预后的潜在生物标志物。
Abstract
Objective To investigate the expression and clinical significance of type Ⅵ collagen alpha 2 chain (COL6A2) in gastric cancer, and to explore the possible underlying mechanisms. Methods Immunohistochemistry was used to detect the expressions of COL6A2 in sixty-two gastric cancer tissues and matched paracancerous tissues. The correlation between COL6A2 expressions and clinicopathological features was analyzed. The survival curve was plotted using the Kaplan-Meier method and validated by the Kaplan-Meier Plotter online database. Data about gastric cancer was downloaded from The Cancer Genome Atlas (TCGA) to analyze the correlation between COL6A2 and epithelial-mesenchymal transition-related protein expressions. Finally, Gene Set Enrichment Analysis (GSEA) was conducted to explore the possible mechanism of COL6A2 in gastric cancer. Results The positive expression rate of COL6A2 in gastric cancer tissues was significantly higher than in matched paracancerous tissues (43.5% vs. 25.8%, P=0.038). High expressions of COL6A2 were significantly correlated with lymph node metastasis, distant metastasis and TNM stage (P<0.05). Consistent with the result of Kaplan-Meier Plotter, survival analysis suggested that gastric cancer patients with high expressions of COL6A2 had a shorter survival time. Meanwhile, COL6A2 was an independent prognostic factor for gastric cancer (HR=2.339, 95% CI: 1.150-4.757, P=0.019). Correlation analysis revealed that COL6A2 expressions were closely related to the expressions of epithelial-mesenchymal transition-related proteins. GSEA showed that high expressions of COL6A2 samples were mainly enriched in several classical signaling pathways including TGF-beta signaling pathway and MAPK signaling pathway. Conclusions COL6A2 is highly expressed in gastric cancer tissues and is associated with poor prognosis. It could be a potential biomarker for the prognosis of gastric cancer patients.
关键词
胃癌 /
Ⅵ型胶原蛋白α2链 /
免疫组化 /
预后
Key words
gastric cancer /
COL6A2 /
immunohistochemistry /
prognosis
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