Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Mol Med Rep. 2018 Oct;18(4):3727-3736. doi: 10.3892/mmr.2018.9368. Epub 2018 Aug 9.
Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer‑associated mortality in the world. However, its mechanisms of occurrence and development have not been clearly elucidated. Furthermore, there is no effective tumor marker for GC. Using DNA microarray analysis, the present study revealed genetic alterations, screened out core genes as novel markers and discovered pathways for potential therapeutic targets. Differentially expressed genes (DEGs) between GC and adjacent normal tissues were identified, followed by pathway enrichment analysis of DEGs. Next, the protein‑protein interaction (PPI) network of DEGs was built and visualized. Analyses of modules in the PPI network were then performed to identify the functional core genes. Finally, survival analysis of core genes was conducted. A total of 256 genes were identified as DEGs between the GC samples and normal samples, including 169 downregulated and 87 upregulated genes. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, the present study identified a total of 143 GO terms and 21 pathways. Six clusters of functional modules were identified, and the genes associated with these modules were screened out as the functional core genes. Certain core genes, including collagen type 12 α1 chain (COL12A1), glutathione S‑transferase α3 (GSTA3), fibrinogen α chain (FGA) and fibrinogen γ chain (FGG), were the first reported to be associated with GC. Survival analysis suggested that these four genes, COL12A1 (P=0.002), GSTA3 (P=3.4x10‑6), FGA (P=0.00075) and FGG (P=1.4x10‑5), were significant poor prognostic factors and therefore, potential targets to improve diagnosis, optimize chemotherapy and predict prognostic outcomes.
胃癌（GC）是全球第五大常见恶性肿瘤，也是癌症相关死亡的第三大主要原因。然而，其发生和发展的机制尚未明确。此外，GC 也没有有效的肿瘤标志物。本研究通过 DNA 微阵列分析，揭示了遗传改变，筛选出核心基因作为新型标志物，并发现了潜在治疗靶点的途径。鉴定了 GC 与相邻正常组织之间的差异表达基因（DEGs），随后对 DEGs 进行通路富集分析。接着构建和可视化了 DEGs 的蛋白质-蛋白质相互作用（PPI）网络。然后对 PPI 网络中的模块进行分析，以确定功能核心基因。最后，对核心基因进行了生存分析。在 GC 样本和正常样本之间共鉴定出 256 个 DEGs，包括 169 个下调基因和 87 个上调基因。通过基因本体论（GO）和京都基因与基因组百科全书通路富集分析，共鉴定出 143 个 GO 术语和 21 个通路。鉴定出 6 个功能模块簇，并筛选出与这些模块相关的基因作为功能核心基因。某些核心基因，包括胶原 12A1 链（COL12A1）、谷胱甘肽 S-转移酶α3（GSTA3）、纤维蛋白原α链（FGA）和纤维蛋白原γ链（FGG），是首次报道与 GC 相关的基因。生存分析表明，COL12A1（P=0.002）、GSTA3（P=3.4x10-6）、FGA（P=0.00075）和 FGG（P=1.4x10-5）这 4 个基因是显著的预后不良因素，因此，它们可能是改善诊断、优化化疗和预测预后的潜在靶点。
