Li Fei, Liang Jiayu, Wei Xin
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, People's Republic of China.
Int J Surg. 2025 Jan 1;111(1):988-997. doi: 10.1097/JS9.0000000000002070.
Clear cell renal cell carcinoma (ccRCC) represents the predominant and remarkably diverse form of renal cell carcinoma. The involvement of the Castor zinc finger 1 (CASZ1) gene in adverse prognostic outcomes has been observed across different cancer types. Nevertheless, the specific altered activities and associated multi-omics characteristics of CASZ1 in ccRCC remain unelucidated.
In order to explore the expression of CASZ1, evaluate its prognostic significance, and aid in the therapeutic decision-making process for patients with ccRCC, The Cancer Genome Atlas (TCGA), Gene expression omnibus (GEO), and The Human Protein Atlas (HPA) databases were utilized to gather data on clinicopathological data, prognostic information, genomic, methylomic and immunomic data. Additionally, the Genomics of Drug Sensitivity in Cancer (GDSC) database provided information on drug sensitivity.
CASZ1 expression was found to be significantly reduced in ccRCC and was associated with unfavorable pathological characteristics and a bleak prognosis. Diminished CASZ1 mRNA levels were notably correlated with heightened cytosine-phosphate-guanine (CpG) methylation, indicating a poorer prognosis for patients with increased methylation. Examination of RNA-seq data from TCGA indicated that the CASZ1-high expression subgroup displayed heightened immune cell infiltration and increased expression of immune checkpoint markers, potentially suggesting a more favorable response to immunotherapy. Furthermore, data from the GDSC database indicated that the CASZ1-low expression subgroup might exhibit greater sensitivity to anti-angiogenetic treatments, such as Sunitinib and Axitinib.
These results indicate that CASZ1 may function as a biomarker for distinguishing various tumor microenvironment phenotypes, predicting prognosis, and assisting in treatment decisions for individuals with ccRCC.
透明细胞肾细胞癌（ccRCC）是肾细胞癌的主要且显著多样的形式。在不同癌症类型中均观察到蓖麻锌指蛋白1（CASZ1）基因与不良预后相关。然而，CASZ1在ccRCC中具体的活性改变及相关多组学特征仍未阐明。
为了探究CASZ1的表达，评估其预后意义，并辅助ccRCC患者的治疗决策过程，利用癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和人类蛋白质图谱（HPA）数据库收集临床病理数据、预后信息、基因组、甲基化组和免疫组学数据。此外，癌症药物敏感性基因组学（GDSC）数据库提供了药物敏感性信息。
发现CASZ1在ccRCC中的表达显著降低，且与不良病理特征和预后不良相关。CASZ1 mRNA水平降低与胞嘧啶-磷酸-鸟嘌呤（CpG）甲基化增加显著相关，表明甲基化增加的患者预后较差。对来自TCGA的RNA测序数据的检查表明，CASZ1高表达亚组显示出免疫细胞浸润增加和免疫检查点标志物表达增加，这可能提示对免疫治疗有更有利的反应。此外，来自GDSC数据库的数据表明，CASZ1低表达亚组可能对抗血管生成治疗（如舒尼替尼和阿昔替尼）更敏感。
这些结果表明，CASZ1可能作为一种生物标志物，用于区分ccRCC患者的各种肿瘤微环境表型、预测预后并辅助治疗决策。
