Meng Lingfeng, Tian Zijian, Long Xingbo, Diao Tongxiang, Hu Maolin, Wang Miao, Zhang Wei, Zhang Yaoguang, Wang Jianye, He Yuhui
Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Genet. 2021 Jan 14;11:600248. doi: 10.3389/fgene.2020.600248. eCollection 2020.
The dysregulation of caspase 4 () expression is related to the occurrence, development, and outcome of many malignant tumors; however, its role in clear cell renal cell carcinoma (ccRCC) remains unclear. Herein, we investigated the expression of in tumor tissues and its relationship with clinical prognosis, immune infiltration, and drug sensitivity status of ccRCC patients. Oncomine and The Cancer Genome Atlas (TCGA) databases were used to determine mRNA expression in ccRCC patients. The correlation between expression and disease prognosis was evaluated using Kaplan-Meier analysis. Related pathways were obtained from TCGA database via gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). Meanwhile, genes co-expressing with in ccRCC were investigated. Finally, we analyzed the proportion of tumor-infiltrating immune cells (TICs) using the CIBERSORT computational method and assessed methylation and its relationship with drug sensitivity. Immunohistochemical analysis of 30 paired ccRCC and adjacent normal tissues confirmed the results. mRNA expression in ccRCC was significantly higher than that in the normal tissues, positively correlated with clinicopathological features (clinical stage and pathological grade), and negatively correlated with patient overall survival (OS). GSEA and GSVA showed that the genes in the -high expression group were primarily enriched in immune-related activities. Moreover, CIBERSORT analysis of TIC proportions revealed that activated CD4 memory T cells were positively correlated with expression. Notably, methylation analysis revealed that the abnormal upregulation of might be caused by hypomethylation. Finally, we found that the abnormal expression of may be related to tumor drug resistance. Overall, our study shows that is overexpressed in ccRCC and is an important factor affecting disease prognosis. Hence, may serve as a potential prognostic biomarker and therapeutic target in ccRCC.
半胱天冬酶4（）表达失调与许多恶性肿瘤的发生、发展及预后相关；然而，其在肾透明细胞癌（ccRCC）中的作用仍不清楚。在此，我们研究了在肿瘤组织中的表达及其与ccRCC患者临床预后、免疫浸润和药物敏感性状态的关系。利用Oncomine和癌症基因组图谱（TCGA）数据库确定ccRCC患者中的mRNA表达。使用Kaplan-Meier分析评估表达与疾病预后的相关性。通过基因集富集分析（GSEA）和基因集变异分析（GSVA）从TCGA数据库中获得相关途径。同时，研究了在ccRCC中与共表达的基因。最后，我们使用CIBERSORT计算方法分析肿瘤浸润免疫细胞（TICs）的比例，并评估甲基化及其与药物敏感性的关系。对30对ccRCC和癌旁正常组织进行免疫组织化学分析证实了结果。ccRCC中的mRNA表达显著高于正常组织，与临床病理特征（临床分期和病理分级）呈正相关，与患者总生存期（OS）呈负相关。GSEA和GSVA表明，高表达组中的基因主要富集于免疫相关活动。此外，对TIC比例的CIBERSORT分析显示，活化的CD4记忆T细胞与表达呈正相关。值得注意的是，甲基化分析显示，的异常上调可能是由低甲基化引起的。最后，我们发现的异常表达可能与肿瘤耐药性有关。总体而言，我们的研究表明，在ccRCC中过表达，是影响疾病预后的重要因素。因此，可能作为ccRCC中潜在的预后生物标志物和治疗靶点。
