CLDN11在结肠癌中的预后价值及其作为潜在免疫治疗靶点的研究

The Prognostic Value of CLDN11 in Colon Cancer and its Potential Immunotherapy Targets

目的分析CLDN11在结肠癌等肿瘤样本中的表达情况,探讨其预后价值及其与常见的免疫治疗靶点基因的相关性。方法利用TIMER2.0在线分析CLDN11在泛癌种中的基因表达情况,分析CLDN11基因的表达与免疫细胞侵润水平的相关性。利用GEPIA2在线分析CLDN11与结肠癌患者总生存时间(OS)和无病生存时间(DFS)的关联,评价其在泛癌种中的预后价值。从TCGA数据库中下载结肠癌相关的mRNA表达数据矩阵和临床信息,分析CLDN11基因的表达在TMN分期和微卫星状态的关系,以及与免疫治疗靶点的相关性。其中,相关性大小用相关性系数(cor)表示。结果CLND11在多种肿瘤包括结肠癌中高表达,在胆管癌(CHOL)和甲状腺癌(THCA)中低表达,且CLDN11的低表达与多种肿瘤患者的良好预后显著相关(P<0.05);Kruskal-wallis检验结果表明,CLDN11的高表达与较高的T分期(P=0.019)、M分期(P=0.0076)、N分期(P=0.0043)、病理分期(P=0.013)和较稳定的微卫星状态(P=5.4e-5)相关。CLDN11的表达与免疫治疗靶点基因CD274、CTLA4、HAVCR2、LAG3、PDCD1、TIGIT的表达显著正相关(cor>0.25,P<0.05)。结论CLDN11可作为多种肿瘤的预后标志物,且可作为结肠癌肿瘤分期的预测因子和潜在的免疫治疗靶点。

Objective To analyze the expression of CLDN11 in colon cancer and other tumor samples,and to explore its prognostic value and its correlation with common immunotherapy target genes.Methods TIMER2.0 was used to analyze the gene expression of CLDN11 in pan-cancer species online,and the correlation between CLDN11 gene expression and immune cell invasion was analyzed.GEPIA2 was used to online analyze the correlation between CLDN11 and total survival time(OS)and disease-free survival time(DFS)of colon cancer patients,and to evaluate its prognostic value in pan-cancer species.Download the mRNA expression data matrix and clinical information related to colon cancer from TCGA database,analyze the relationship between CLDN11 gene expression in TMN stage and microsatellite status,and the correlation with immunotherapy targets.where the correlation was expressed by the correlation coefficient(cor).Results CLND11 was highly expressed in various tumors,including colon cancer,and lowly expressed in cholangiocarcinoma(CHOL)and thyroid cancer(THCA).The low expression of CLDN11 was significantly correlated with the good prognosis of patients with various tumors(P<0.05).The Kruskal-wallis test results showed that the high expression of CLDN11 was related to higher T staging(P=0.019),M staging(P=0.0076),N staging(P=0.0043),pathological staging(P=0.013)and stable microsatellite status(P=5.4e-5).The expression of CLDN11 was significantly positively correlated with the expression of CD274,CTLA4,HAVCR2,LAG3,PDCD1 and TIGIT(cor>0.25,P<0.05).Conclusion CLDN11 can be used as a prognostic marker for a variety of tumors,and can be used as a predictor of tumor staging of colon cancer and a potential target for immunotherapy.