Zhang Lihua, Jiang Xin, Li Yan, Fan Qianqian, Li Hongjuan, Jin Linfang, Li Liqi, Jin Yufen, Zhang Ting, Mao Yong, Hua Dong
Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China.
School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
Front Oncol. 2020 Aug 28;10:1504. doi: 10.3389/fonc.2020.01504. eCollection 2020.
Wnt2 mRNA is widely expressed in various tumor tissues. Wnt2 overexpression promotes tumor growth, migration, invasion, and metastasis. However, its underlying molecular action mechanisms and clinical implications in colon adenocarcinoma (COAD) remain unclear. mRNA expression data, obtained from tissue samples, and pathophysiological data of 368 COAD patients were obtained from the Cancer Genome Atlas (TCGA) database. Further, Pearson's correlation analysis was performed to explore the correlation between the expression levels of Wnt2 and other genes in the human genome. Subsequently, a protein-protein interaction (PPI) network was constructed for hub gene identification. Overall survival and significance were determined by Kaplan-Meier analysis, and the log-rank test was used to further identify genes with prognostic significance in COAD from GEO datasets (GSE17538 and GSE39582). Subsequently, 158 tissue samples from Affiliated Hospital of Jiangnan University were used for expression verification. Gene set enrichment analysis (GSEA) was performed on high and low Wnt2 expression datasets to identify potential signaling pathways activated in COAD. In all, 10 hub genes associated with Wnt2 were screened by Pearson's correlation analysis and PPI network, with Wnt2 and COL8A1 having significantly poor prognosis by Kaplan-Meier analysis and log-rank test. Furthermore, high expressions of COL8A1 and Wnt2 were associated with poor survival both in TCGA and GEO cohorts. We further found a correlation between the expressions of Wnt2 and COL8A1 in COAD as per immunohistochemical analysis. To further elucidate the underlying molecular mechanisms of Wnt2 in COAD, we searched for pathways enriched in Wnt2 overexpressing datasets by GSEA. Our findings revealed that high Wnt2 levels were significantly associated with extracellular matrix receptor and focal adhesion pathways. Wnt2 expression correlated with COL8A1 expression in COAD; patients with high Wnt2 and COL8A1 expressions had worse survival outcomes. Pathways identified in this study prompt the molecular role of Wnt2 in COAD and provide directions to further elucidate the involved molecular mechanisms in COAD.
Wnt2信使核糖核酸在各种肿瘤组织中广泛表达。Wnt2过表达促进肿瘤生长、迁移、侵袭和转移。然而，其在结肠腺癌（COAD）中的潜在分子作用机制和临床意义仍不清楚。从癌症基因组图谱（TCGA）数据库中获取了368例COAD患者的组织样本mRNA表达数据和病理生理数据。此外，进行了Pearson相关性分析，以探索Wnt2与人类基因组中其他基因表达水平之间的相关性。随后，构建了蛋白质-蛋白质相互作用（PPI）网络以识别枢纽基因。通过Kaplan-Meier分析确定总生存期和显著性，并使用对数秩检验从GEO数据集（GSE17538和GSE39582）中进一步鉴定COAD中具有预后意义的基因。随后，使用江南大学附属医院的158份组织样本进行表达验证。对高Wnt2表达数据集和低Wnt2表达数据集进行基因集富集分析（GSEA），以识别COAD中激活的潜在信号通路。通过Pearson相关性分析和PPI网络共筛选出10个与Wnt2相关的枢纽基因，通过Kaplan-Meier分析和对数秩检验发现Wnt2和COL8A1的预后显著较差。此外，在TCGA和GEO队列中，COL8A1和Wnt2的高表达均与较差的生存率相关。根据免疫组织化学分析，我们进一步发现COAD中Wnt2和COL8A1的表达之间存在相关性。为了进一步阐明Wnt2在COAD中的潜在分子机制，我们通过GSEA搜索Wnt2过表达数据集中富集的通路。我们的研究结果表明，高Wnt2水平与细胞外基质受体和粘着斑通路显著相关。COAD中Wnt2表达与COL8A1表达相关；Wnt2和COL8A1高表达的患者生存结果更差。本研究中确定的通路提示了Wnt2在COAD中的分子作用，并为进一步阐明COAD中涉及的分子机制提供了方向。
