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铁死亡相关基因 CHAC1 是肾透明细胞癌不良预后的有效指标。

Ferroptosis-related gene CHAC1 is a valid indicator for the poor prognosis of kidney renal clear cell carcinoma.

机构信息

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Nursing Department, Wujiang Fifth People's Hospital, Suzhou, China.

出版信息

J Cell Mol Med. 2021 Apr;25(7):3610-3621. doi: 10.1111/jcmm.16458. Epub 2021 Mar 16.

Abstract

To evaluate the validity of CHAC1 for predicting the prognosis of kidney renal clear cell carcinoma (KIRC) and to explore its therapeutic potential for KIRC, we conducted several bioinformatic analyses using the sequencing data and clinical information derived from online databases. We found CHAC1 is down-regulated in KIRC samples when compared with normal samples but up-regulated in KIRC samples with relatively higher malignancy and later stages. Univariate cox analysis and multivariate cox regression analysis were conducted and the results revealed up-regulated CHAC1 is an independent risk factor for poor prognosis of KIRC. Further, the nomogram model based on the result of multivariate cox regression analysis was constructed and effectively predicted patients' 1-year, 3-year and 5-year survival respectively. The correlation analyses showed CHAC1 is associated with the immune pathway markers of memory B cell, natural killer cell and type1 T helper cell as well as the checkpoint genes like ADORA2A, CD200, CD44, CD70, HHLA2, NRP1, PDCD1LG2 and TNFRSF18. Furthermore, experiments in vitro indicated CHAC1 could induce cell death in KIRC cell lines but had limited influence on cell migration and cell invasion. In conclusion, CHAC1 is found a valid indicator for poor prognosis of kidney renal clear cell carcinoma.

摘要

为了评估 CHAC1 预测肾透明细胞癌(KIRC)预后的有效性,并探讨其对 KIRC 的治疗潜力,我们使用来自在线数据库的测序数据和临床信息进行了几项生物信息学分析。我们发现,与正常样本相比,CHAC1 在 KIRC 样本中下调,但在恶性程度较高和晚期的 KIRC 样本中上调。进行了单变量 Cox 分析和多变量 Cox 回归分析,结果表明上调的 CHAC1 是 KIRC 预后不良的独立危险因素。此外,还基于多变量 Cox 回归分析的结果构建了列线图模型,并有效地分别预测了患者的 1 年、3 年和 5 年生存率。相关性分析表明,CHAC1 与记忆 B 细胞、自然杀伤细胞和 1 型 T 辅助细胞的免疫途径标志物以及 ADORA2A、CD200、CD44、CD70、HHLA2、NRP1、PDCD1LG2 和 TNFRSF18 等检查点基因相关。此外,体外实验表明,CHAC1 可诱导 KIRC 细胞系死亡,但对细胞迁移和细胞侵袭的影响有限。总之,CHAC1 被发现是肾透明细胞癌预后不良的有效指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94d/8034464/e055a4510ae5/JCMM-25-3610-g003.jpg

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