结直肠癌预后分子标志物WNT10B及WNT家族对结直肠癌的影响

WNT10B as a new prognostic molecular marker for colorectal cancer and the effect of Wnt family on the progression of colorectal cancer

目的:探讨WNT10B对结直肠癌预后的影响和分子机制以及WNT家族对结直肠癌进展的影响。方法:采用癌症和肿瘤基因图谱(TCGA)中结直肠癌与癌旁47对样本的m RNA表达数据分析WNT家族差异表达基因,对差异基因501例结直肠癌样本进行总生存期和无复发生存期的生存分析,并对预后有影响的基因进行年龄、性别、临床分期的多因素校正预后分析及临床病理特征的相关性分析,最后进行基因富集分析(GSEA)确定分子通路。结果:WNT家族中的WNT2、WNT2B、WNT3、WNT5A、WNT5B、WNT6、WNT9A、WNT10A、WNT10B和WNT16共10个基因在癌与癌旁组织差异有统计学意义(P<0.01),其中WNT5A和WNT10B对于总生存期有显著影响(P<0.05),WNT10A和WNT10B对于无复发生存期有显著影响(P<0.01);WNT10B校正年龄、性别、临床分期之后,对总生存期(P=0.003)和无复发生存期(P=0.08)影响仍然有统计学意义;WNT10B表达水平与患者肿瘤大小、淋巴结转移有关(P<0.05),与其他临床病理特征无关(P>0.05);神经活性的配体-受体相互作用信号通路和细胞黏附分子通路可能是WNT10B影响结直肠癌预后的重要分子通路。结论:WNT家族对于结直肠癌的进展有重要的影响,其中WNT10B对于总生存期和无复发生存期影响显著,可以作为结直肠癌诊断和预后的分子标志物。

Objectivez To investigate the effect of WNT10B on the prognosis of colorectal cancer and its molecular mechanism and the effect of WNT family on the progression of colorectal cancer. Methods： Analysis of differentially expressed genes in Wnt family by using the mRNA ex- pression data of The Cancer Genome Atlas （TCGA） with 47 pairs of cancer, overall survival and re- currence-free survival analysis of differential genes were performed with 501 cases of colorectal cancer. Multivariate prognostic analysis adjusted for age, sex, clinical stage and correlation analysis of clinicopathological features were performed using significant genes for survival. Finally, gene set enrichment analysis （GSEA） was performed to determine the molecular pathways. Resuils： A total of 10 genes including WNT2, WNT2B, WNT3, WNTSA, WNT5B, WNT6, WNT9A, WNT10A, WNT10B, WNT16 among the WNT family had statistically significant differences in cancer and asia- cent normal tissue （P〈0.01）, among them, both WNT5A and WNT10B had significant effects on total survival（P〈0.05）, WNTIOA and WNT10B were significant for recurrence-free survival（P〈0.01）; After adjusting for age, sex and clinical stage, WNT10B was still statistically significant for overall survival （P=0.003） and recurrence-free survival （p=0.08）; WNT10B expression level was related to tumor size and lymph node metastasis（P〈0.05）, unrelated to other clinicopathological features; Neuroactive lig- and-receptor interaction pathway and Cell adhesion molecules（CAMs） pathway may be the molecu- lar pathway that WNT10B affects the prognosis of colorectal cancer. Conclusion： The WNT family has an important effect on the progression of colorectal cancer, in which WNT10B has a significant effect on overall survival and recurrence-free survival, and can be used as a molecular biomarker for the diaQnosis and Droanosis of colorectal cancer.