Identification and validation of AFAP1L1 as an immune-related prognostic biomarker in clear cell renal cell carcinoma.

IF 1.9 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biomarkers Pub Date : 2026-03-23 DOI:10.1080/1354750X.2026.2630072

Qiaoping Yan, Binbin Zhang, Yunhan Yu, Yuewen Si, Yuan Zhang, Zijian Ye, Qingming Zhang, Wenling Wu, Xuegang Luo, Biao Xie

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引用次数: 0

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) accounts for over 75% of all renal cancer and contributes significantly to cancer-associated mortality. This study aims to identify a new ccRCC biomarker.

Methods: Univariate and multivariate Cox regression models were performed for prognostic analysis. Differentially expressed genes (DEGs) were identified based on high and low expression AFAP1L1 groups. Functional enrichment analysis was conducted on the DEGs. Immunoassays were conducted on immune checkpoints, immune cells, and other components. Single-cell expression of AFAP1L1, along with associated pseudo-temporal trajectory analyses, was evaluated. The Connectivity Map was employed to identify potentially small-molecules. AFAP1L1 mRNA expression was measured via quantitative real-time PCR (qRT-PCR) experiment.

Results: AFAP1L1 was significantly upregulated in training cohort and qRT-PCR, and lower expression level was correlated with shorter overall survival, which was also confirmed in E-MTAB-1980 and CPTAC validation cohorts. The upregulated DEGs were primarily involved in signaling pathways, nephron development, and transporter activity. AFAP1L1 was positively related with neutrophils and macrophages. AFAP1L1 exhibited a relatively higher expression level in endothelial cells at the single-cell level. Five potential therapeutic agents targeting ccRCC were identified.

Conclusions: AFAP1L1 may impact the ccRCC development and progression, acting as an immune-related prognostic marker for ccRCC.

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AFAP1L1在透明细胞肾细胞癌中作为免疫相关预后生物标志物的鉴定和验证

背景：透明细胞肾细胞癌（ccRCC）占所有肾癌的75%以上，是癌症相关死亡率的重要因素。本研究旨在鉴定一种新的ccRCC生物标志物。方法：采用单因素和多因素Cox回归模型进行预后分析。根据AFAP1L1高表达和低表达组鉴定差异表达基因（DEGs）。对deg进行功能富集分析。对免疫检查点、免疫细胞和其他成分进行免疫测定。评估AFAP1L1的单细胞表达，以及相关的伪时间轨迹分析。连接图被用来识别潜在的小分子。采用实时荧光定量PCR （qRT-PCR）检测AFAP1L1 mRNA的表达。结果：AFAP1L1在训练队列和qRT-PCR中显著上调，表达水平越低，总生存期越短，这在E-MTAB-1980和CPTAC验证队列中也得到证实。上调的deg主要参与信号通路、肾元发育和转运蛋白活性。AFAP1L1与中性粒细胞和巨噬细胞呈正相关。在单细胞水平上，AFAP1L1在内皮细胞中的表达水平相对较高。确定了5种靶向ccRCC的潜在治疗药物。结论：AFAP1L1可能影响ccRCC的发生和进展，可作为ccRCC的免疫相关预后标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomarkers 医学-毒理学

CiteScore

5.00

自引率

3.80%

发文量

140

审稿时长

3 months

期刊介绍： The journal Biomarkers brings together all aspects of the rapidly growing field of biomarker research, encompassing their various uses and applications in one essential source. Biomarkers provides a vital forum for the exchange of ideas and concepts in all areas of biomarker research. High quality papers in four main areas are accepted and manuscripts describing novel biomarkers and their subsequent validation are especially encouraged: • Biomarkers of disease • Biomarkers of exposure • Biomarkers of response • Biomarkers of susceptibility Manuscripts can describe biomarkers measured in humans or other animals in vivo or in vitro. Biomarkers will consider publishing negative data from studies of biomarkers of susceptibility in human populations.