Elementary screening of lymph node metastatic-related genes in gastric cancer based on the co-expression network of messenger RNA, microRNA and long non-coding RNA

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The high mortality might be attributed to delay in detection and is closely related to lymph node metastasis. Therefore, it is of great importance to explore the mechanism of lymph node metastasis and find strategies to block GC metastasis. Messenger RNA (mRNA), microRNA (miRNA) and long non-coding RNA (lncRNA) expression data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 908 differentially expressed factors with variance >0.5 including 542 genes, 42 miRNA, and 324 lncRNA were screened using significant analysis microarray algorithm, and interaction networks were constructed using these differentially expressed factors. Furthermore, we conducted functional modules analysis in the network, and found that yellow and turquoise modules could separate samples efficiently. The groups classified in the yellow and turquoise modules had a significant difference in survival time, which was verified in another independent GC mRNA dataset (GSE62254). The results suggested that differentially expressed factors in the yellow and turquoise modules may participate in lymph node metastasis of GC and could be applied as potential biomarkers or therapeutic targets for GC.

胃癌（gastric cancer, GC）是全球范围内第五大常见恶性肿瘤，亦是癌症相关死亡的第三大诱因。其高死亡率或归因于诊断延迟，且与淋巴结转移密切相关。因此，阐明淋巴结转移的发生机制并探寻阻断胃癌转移的策略具有重要意义。研究团队从癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库下载了信使RNA（Messenger RNA, mRNA）、微小RNA（microRNA, miRNA）以及长链非编码RNA（long non-coding RNA, lncRNA）的表达数据与临床信息。通过显著性微阵列分析算法筛选出方差大于0.5的差异表达因子共908个，其中包含542个基因、42个miRNA、324个lncRNA，并基于上述差异表达因子构建了相互作用网络。进一步对该网络开展功能模块分析，结果显示黄色模块与绿松石模块可有效区分样本。归类于黄色模块与绿松石模块的样本组在生存时间上存在显著差异，该结论在另一独立胃癌mRNA数据集GSE62254中得到验证。本研究结果表明，黄色模块与绿松石模块中的差异表达因子可能参与胃癌的淋巴结转移过程，有望作为胃癌潜在的生物标志物或治疗靶点。