Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG.
Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG.
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DOI：
10.3892/mmr.2018.9368
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发表时间：
2018-10
影响因子：
3.4
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Duan S;Gong B;Wang P;Huang H;Luo L;Liu F
胃癌（GC）是世界上第五大常见恶性肿瘤，也是癌症相关死亡的第三大原因。但其发生发展机制尚未完全阐明。此外，没有有效的肿瘤标记物GC。利用DNA微阵列分析，本研究揭示了遗传改变，筛选出核心基因作为新的标记，并发现了潜在的治疗靶点的途径。对胃癌与癌旁正常组织中的差异表达基因进行了鉴定，并对差异表达基因进行了途径富集分析。接下来，构建并可视化DEG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鉴定功能核心基因。最后，进行核心基因的存活分析。在胃癌组和正常对照组中共检测到256个差异表达基因，其中下调基因169个，上调基因87个。通过对基因本体（GO）和京都基因与基因组百科全书（Encyclopedia of Genes and Genomes pathway）的富集分析，本研究共识别出143个GO术语和21条通路。鉴定了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12型胶原α1链（COL 12 A1）、谷胱甘肽S-转移酶α3（GSTA 3）、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，这四个基因，COL 12 A1（P=0.002），GSTA 3（P=3.4×10 - 6），FGA（P=0.00075）和FGG（P=1.4×10-5），是显著的不良预后因素，因此，潜在的目标，以改善诊断，优化化疗和预测预后结果。
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=3.4×10−6), FGA (P=0.00075) and FGG (P=1.4×10-5), were significant poor prognostic factors and therefore, potential targets to improve diagnosis, optimize chemotherapy and predict prognostic outcomes.
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