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生物信息学分析和回顾性临床研究确定DNAJB4作为一种泛癌生物标志物,重点关注肾癌。

Bioinformatic analysis and retrospective clinical study identifying DNAJB4 as a pan-cancer biomarker with a highlight on kidney cancer.

作者信息

Chu Chuanmin, Lu Bingnan, Fu Wenjia, Li Muchen, Dong Keqin, Lyu Donghao, Yao Yuntao, Li Yuanan, Liu Yifan, Pan Xiuwu, Chen Ming

机构信息

Department of Urology, Zhongda Hospital Affiliated to Southeast University, Nanjing, 210000, China.

Department of Urology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, China.

出版信息

Clin Exp Med. 2025 Jul 22;25(1):260. doi: 10.1007/s10238-025-01806-9.

Abstract

DNAJB4 plays a crucial role in tumor suppression and proteostasis across various cancers. However, a comprehensive pan-cancer analysis of DNAJB4 remains lacking. We performed an extensive pan-cancer analysis to assess DNAJB4 expression and its clinical value. Analyses included competing endogenous RNA, protein-protein interaction networks, tumor purity, genomic profiling, immune microenvironment evaluation, and drug sensitivity. Gene set enrichment analysis was used to identify key pathways associated with DNAJB4. Additionally, DNAJB4 expression was evaluated in a cohort of 370 kidney neoplasm patients using immunohistochemistry to explore its clinical significance. DNAJB4 expression was significantly lower in tumor tissues compared to normal tissues in pan-cancer analysis. Reduced expression of DNAJB4 correlated with clinical outcomes, tumor purity, genomic alterations, immune microenvironment features, and drug sensitivity. In kidney neoplasm patients, DNAJB4 expression was significantly lower in tumor tissues (P value < 0.001) and was associated with poor prognosis, including progression-free survival (P value < 0.01) and overall survival (P value < 0.05). Higher DNAJB4 levels were linked to advanced tumor stages (P value < 0.001 for T2b-T4, P value < 0.01 for stages 3-4). DNAJB4 serves as a multifunctional biomarker in pan-cancer, particularly in kidney neoplasm, and is closely related to tumorigenesis, staging, and prognosis. Targeting DNAJB4 could provide new therapeutic avenues for cancer treatment.

摘要

DNAJB4在多种癌症的肿瘤抑制和蛋白质稳态中发挥着关键作用。然而,目前仍缺乏对DNAJB4的全面泛癌分析。我们进行了广泛的泛癌分析,以评估DNAJB4的表达及其临床价值。分析内容包括竞争性内源性RNA、蛋白质-蛋白质相互作用网络、肿瘤纯度、基因组分析、免疫微环境评估和药物敏感性。基因集富集分析用于识别与DNAJB4相关的关键通路。此外,我们使用免疫组织化学方法在370例肾肿瘤患者队列中评估了DNAJB4的表达,以探讨其临床意义。在泛癌分析中,肿瘤组织中DNAJB4的表达明显低于正常组织。DNAJB4表达降低与临床结局、肿瘤纯度、基因组改变、免疫微环境特征和药物敏感性相关。在肾肿瘤患者中,肿瘤组织中DNAJB4的表达明显较低(P值<0.001),并与不良预后相关,包括无进展生存期(P值<0.01)和总生存期(P值<0.05)。较高的DNAJB4水平与肿瘤晚期相关(T2b-T4的P值<0.001,3-4期的P值<0.01)。DNAJB4在泛癌中,尤其是在肾肿瘤中,作为一种多功能生物标志物,与肿瘤发生、分期和预后密切相关。靶向DNAJB4可为癌症治疗提供新的治疗途径。

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