标题：基于数据挖掘分析基因在肾透明细胞癌的表达及临床意义

      作者：徐争光，李灿楦，李晓，林晏廷，陈洁    暨南大学附属第一医院泌尿外科，广东 广州 510630

      卷次： 2021年32卷20期

      【摘要】 目的 探索CLDN10在肾透明细胞癌(ccRCC)的表达及临床意义。方法 通过Oncomine数据库、Ualcan数据库、GEPIA数据库、HPA数据库、String-DB数据库、Metascape数据库分析CLDN10在正常肾组织与ccRCC中的表达差异、CLDN10表达水平与 ccRCC患者临床特征的相关性及其对患者预后的影响、CLDN10在正常肾组织与 ccRCC的甲基化水平差异、CLDN10与上下游蛋白的相互作用关系以及关联基因的富集通路。结果 CLDN10在ccRCC中的mRNA和蛋白质表达水平较正常肾组织低(P<0.05)，利用Ualcan数据库分析发现CLDN10在正常肾组织与肿瘤分期(stage1、stage2、stage3和 stage4)、ccRCC亚型(ccA和 ccB)、淋巴结转移(N0和N1)的表达差异均为P<1E-12 (P<0.05)，且随着肿瘤分期的增高，CLDN10的表达呈下降趋势，其表达水平与肿瘤进展相关，CLDN10低表达患者生存率较高表达组明显降低(P<0.05)。CLDN10在正常肾组织与 stage1、stage2、stage3、stage4中的甲基化表达差异分别为P=1.62E-12、P=3.11E-08、P=1.62E-12、P=1.62E-12，以上差异均具有统计学意义(P<0.05)。同时，与CLDN10蛋白相关的蛋白有CLDN14、CLDN2、CLDN16、CLDN8、CLDN3、CLDN1、CLDN19等，主要参与了增殖、分化、转移、细胞屏障、细胞紧密连接等生物过程。结论 通过挖掘分析肿瘤生物信息数据库发现CLDN10在 ccRCC中低表达，且其表达水平与肿瘤进展和患者预后相关，为后续研究 ccRCC的诊断标志物和治疗靶点提供理论依据。
      【关键词】 CLDN10；肾透明细胞癌；生物信息学；表达差异；预后
      【中图分类号】 R737.11 【文献标识码】 A 【文章编号】 1003—6350（2021）20—2589—08

Analysis of CLDN10 gene expression and clinical significance in clear cell renal cell carcinoma based on datamining.
XU Zheng-guang, LI Can-xuan, LI Xiao, LIN Yan-ting, CHEN Jie. Department of Urology Surgery, the FirstAffiliated Hospital of Jinan University, Guangzhou 510630, Guangdong, CHINA
【Abstract】 Objective To explore the expression and clinical significance of CLDN10 in clear cell renal cellcarcinoma (ccRCC). Methods The expression differences of CLDN10 in normal kidney tissue and ccRCC were ana-lyzed through Oncomine, Ualcan, GEPIA, HPA, String-DB, and Metascape database, as well as the correlation betweenCLDN10 expression level and the clinical characteristics of ccRCC patients and its influence on the prognosis of pa-tients, the difference in methylation level of CLDN10 between normal kidney tissue and ccRCC, the interaction betweenCLDN10 and upstream and downstream proteins, and the enrichment pathway of CLDN10 related genes. Results ThemRNA and protein expression levels of CLDN10 were lower in ccRCC tissues than in normal kidney tissues (P<0.05).Ualcan database analysis revealed that CLDN10 expression differences between normal kidney tissue and different tu-mor stages (stage1, stage2, stage3, and stage4), and ccRCC subtypes (ccA and ccB), and lymph node metastasis (N0 andN1) were all P<1E-12 (P<0.05). With the increase of tumor stage, the CLDN10 expression showed a downward trend,its expression level was related to tumor progression, and the survival rate of patients with low CLDN10 expression wassignificantly lower than that of patients with high expression (P<0.05). The differences in methylation expression ofCLDN10 between normal kidney tissue and different tumor stages (stage1, stage2, stage3, and stage4) were P=1.62E-12,P=3.11E-08, P=1.62E-12, P=1.62E-12, respectively, all differences were statistically significant (P<0.05). Meanwhile,the proteins related to CLDN10 included CLDN14, CLDN2, CLDN16, CLDN8, CLDN3, CLDN1, and CLDN19, whichwere mainly involved in biological processes such as proliferation, differentiation, metastasis, cell barrier, and cell tightjunctions. Conclusion Through mining and analyzing the tumor bioinformatics database, it is found that CLDN10 isunder-expressed in ccRCC, its expression level is related to tumor progression and patient prognosis, which provides atheoretical basis for subsequent research on diagnostic markers and therapeutic targets of ccRCC.
      【Key words】 CLDN10; Clear cell renal cell carcinoma; Bioinformatics; Expression differences; Prognosis