The dysregulation of caspase 4 (CASP4) 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 CASP4 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 CASP4 mRNA expression in ccRCC patients. The correlation between CASP4 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 CASP4 in ccRCC were investigated. Finally, we analyzed the proportion of tumor-infiltrating immune cells (TICs) using the CIBERSORT computational method and assessed CASP4 methylation and its relationship with drug sensitivity. Immunohistochemical analysis of 30 paired ccRCC and adjacent normal tissues confirmed the in silico results. CASP4 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 CASP4-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 CASP4 expression. Notably, methylation analysis revealed that the abnormal upregulation of CASP4 might be caused by hypomethylation. Finally, we found that the abnormal expression of CASP4 may be related to tumor drug resistance. Overall, our study shows that CASP4 is overexpressed in ccRCC and is an important factor affecting disease prognosis. Hence, CASP4 may serve as a potential prognostic biomarker and therapeutic target in ccRCC.

caspase 4（CASP4）表达与许多恶性肿瘤的发生，发展和结果有关；但是，其在透明细胞肾细胞癌（ccRCC）中的作用仍不清楚。在这里，我们研究了CASP4ccRCC患者的肿瘤组织中的α-转移酶及其与临床预后，免疫浸润和药物敏感性状况的关系。Oncomine和癌症基因组图谱（TCGA）数据库用于确定CASP4ccRCC患者中的mRNA表达。之间的相关性CASP4表达和疾病预后使用Kaplan-Meier分析进行评估。通过基因组富集分析（GSEA）和基因组变异分析（GSVA）从TCGA数据库获得相关途径。同时，基因与CASP4在ccRCC中进行了调查。最后，我们使用CIBERSORT计算方法分析了肿瘤浸润免疫细胞（TIC）的比例，并进行了评估CASP4甲基化及其与药物敏感性的关系。对30个配对的ccRCC及其邻近正常组织的免疫组织化学分析确认在计算机上 结果。 CASP4ccRCC中的mRNA表达显着高于正常组织，与临床病理特征（临床分期和病理分级）呈正相关，与患者总体生存率（OS）呈负相关。GSEA和GSVA表明CASP4-高表达组主要富含免疫相关活性。此外，CIBERSORT对TIC比例的分析表明，活化的CD4记忆T细胞与T4呈正相关。CASP4表达。值得注意的是，甲基化分析显示，其异常上调CASP4可能是由甲基化不足引起的。最后，我们发现CASP4可能与肿瘤的耐药性有关。总体而言，我们的研究表明CASP4在ccRCC中过表达，是影响疾病预后的重要因素。因此，CASP4 可以作为ccRCC中潜在的预后生物标志物和治疗靶标。