State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China,
World J Gastroenterol. 2019 Aug 21;25(31):4452-4467. doi: 10.3748/wjg.v25.i31.4452.
Adenoma polyposis coli () mutation is associated with tumorigenesis the Wnt signaling pathway.
To investigate the clinical features and mechanism of expression in gastric cancer (GC).
Based on expression profile, the related genome-wide mRNA expression, microRNA (miRNA) expression, and methylation profile in GC, the relationship between and GC, as well as the prognostic significance of were systematically analyzed by multi-dimensional methods.
We found that high expression of ( ) was significantly associated with adverse outcomes of T4 GC patients. Genome-wide gene expression analysis revealed that varying expression levels in GC were associated with some important oncogenes, and corresponding cellular functional pathways. Genome-wide miRNA expression analysis indicated that most of miRNAs associated with high expression were downregulated. The mRNA-miRNA regulatory network analysis revealed that down-regulated miRNAs affected their inhibitory effect on tumor genes. Genome-wide methylation profiles associated with expression showed that there was differential methylation between the and groups. The number of hypermethylation sites was larger than that of hypomethylation sites, and most of hypermethylation sites were enriched in CpG islands.
Our research demonstrated that high expression is an unfavorable prognostic factor for T4 GC patients and may be used as a novel biomarker for pathogenesis research, diagnosis, and treatment of GC.
腺瘤性结肠息肉病 () 突变与 Wnt 信号通路相关的肿瘤发生有关。
研究结肠癌（GC）中表达的临床特征和机制。
基于表达谱，对 GC 相关的全基因组 mRNA 表达、微小 RNA（miRNA）表达和甲基化谱进行多维方法的系统分析，研究与 GC 的关系以及表达的预后意义。
我们发现高表达（）与 T4GC 患者不良结局显著相关。全基因组基因表达分析显示，GC 中表达水平的变化与一些重要的癌基因和相应的细胞功能途径有关。全基因组 miRNA 表达分析表明，与高表达相关的大多数 miRNA 下调。mRNA-miRNA 调控网络分析表明，下调的 miRNA 影响其对肿瘤基因的抑制作用。与表达相关的全基因组甲基化谱显示，与表达相关的甲基化差异。超甲基化位点的数量多于低甲基化位点，且大多数超甲基化位点富集在 CpG 岛中。
我们的研究表明，高表达是 T4GC 患者不良预后的一个不利因素，可能作为 GC 发病机制研究、诊断和治疗的新型生物标志物。
