Chen Meilin, Tang Xiuxin, Liang YanPing, Ding Tangdang, He Meifang, Wang Dong, Wang Ruizhi
The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Technol Cancer Res Treat. 2025 Jan-Dec;24:15330338251330791. doi: 10.1177/15330338251330791. Epub 2025 Mar 31.
IntroductionRenal cancer, particularly Kidney Renal Clear Cell Carcinoma (KIRC), remains a major clinical challenge due to its aggressive nature and poor prognosis. Identifying reliable biomarkers for tumor progression and survival is critical for improving patient outcomes. This study aimed to investigate the role of Centromere Protein F (CENPF) as a potential prognostic biomarker for renal cancer.MethodData from the TCGA database, including Kidney Chromophobe (KICH), Kidney Renal Papillary Cell Carcinoma (KIRP), and KIRC, were analyzed to identify differentially expressed genes. Molecular Complex Detection (MCODE) was used to identify significant gene modules among upregulated genes, and univariate Cox regression analyses assessed the prognostic value of hub genes. Retrospective qPCR was conducted on tissue and plasma samples from KIRC patients to validate findings. Single-cell sequencing data from the GSE159115 dataset were analyzed, and the CIBERSORT algorithm was applied to evaluate the composition of tumor immune infiltrating cells (TIICs).ResultsCENPF was identified as a hub gene significantly upregulated in renal cancer subtypes, with overexpression linked to worse survival outcomes in KIRC patients. Retrospective qPCR confirmed high CENPF expression was associated with poorer prognosis. Single-cell sequencing revealed that CENPF is predominantly expressed in T-cell clusters. TIIC analysis showed a negative correlation between CENPF and resting mast cells, but positive correlations with follicular helper T-cells and memory-activated CD4T-cells. Prognostic analysis indicated that high follicular helper T-cell expression predicted poorer survival, while high plasma cell expression correlated with better outcomes.ConclusionCENPF plays a critical role in tumor progression and the modulation of the tumor immune microenvironment in KIRC. These findings suggest that CENPF could serve as a valuable prognostic biomarker and potential target for therapeutic intervention in renal cancer.
引言
肾癌，尤其是肾透明细胞癌（KIRC），因其侵袭性和预后不良，仍然是一个重大的临床挑战。识别可靠的肿瘤进展和生存生物标志物对于改善患者预后至关重要。本研究旨在探讨着丝粒蛋白F（CENPF）作为肾癌潜在预后生物标志物的作用。
方法
分析来自TCGA数据库的数据，包括肾嫌色细胞癌（KICH）、肾乳头状细胞癌（KIRP）和KIRC，以确定差异表达基因。使用分子复合物检测（MCODE）来识别上调基因中的重要基因模块，并通过单变量Cox回归分析评估枢纽基因的预后价值。对KIRC患者的组织和血浆样本进行回顾性qPCR以验证结果。分析来自GSE159115数据集的单细胞测序数据，并应用CIBERSORT算法评估肿瘤免疫浸润细胞（TIIC）的组成。
结果
CENPF被确定为在肾癌亚型中显著上调的枢纽基因，其过表达与KIRC患者较差的生存结果相关。回顾性qPCR证实CENPF高表达与较差的预后相关。单细胞测序显示CENPF主要在T细胞簇中表达。TIIC分析显示CENPF与静息肥大细胞呈负相关，但与滤泡辅助性T细胞和记忆激活的CD4T细胞呈正相关。预后分析表明，高滤泡辅助性T细胞表达预示着较差的生存，而高浆细胞表达与较好的结果相关。
结论
CENPF在KIRC的肿瘤进展和肿瘤免疫微环境调节中起关键作用。这些发现表明，CENPF可作为有价值的预后生物标志物和肾癌治疗干预的潜在靶点。
