SKA1在肾透明细胞癌中的生物学特征及与临床特征的相关性^*

To analyze the biological characteristics and clinical relevance of spindle and kinetochore-associated complex 1(SKA1) in renal clear cell carcinoma

摘要

目的 探讨纺锤体-着丝粒相关复合物亚基1(SKA1)在肾透明细胞癌中的生物学特征及与临床特征的相关性。方法 首先,应用癌症基因组图谱(TCGA)和基因型-组织表达数据库(GTEx)中的测序数据分析了SKA1在泛癌中的表达差异;其次,收集肾透明细胞癌的临床术后样本,包括癌区的肿瘤组织和邻近非肿瘤组织,应用实时荧光定量聚合酶链式反应和Western blot法定量分析SKA1的mRNA和蛋白的表达情况;最后,应用ROC曲线、Kaplan-Meier生存曲线以及Cox比例风险分析了SKA1对肾透明细胞癌的诊断效能和预后价值,并构建了SKA1蛋白互作网络进行功能富集分析。结果 表达上调的SKA1在泛癌水平上表现出显著的促癌作用;来源于临床样本的试验验证结果显示,与邻近非肿瘤组织比较,SKA1在肾透明细胞癌组织中的蛋白表达和mRNA表达均显著升高(P＜0.01);SKA1表达的上调促进了肾透明细胞癌的恶性进展,并与侵袭性临床病理特征相关。蛋白互作及富集分析提示SKA1可能通过影响有丝分裂过程加快细胞周期及增殖相关机制起到促癌的作用。结论 SKA1在肾透明细胞癌中显著高表达,SKA1是一个促癌基因,与肾透明细胞癌的不良预后显著相关,且具有较好的诊断效能。

Abstract

Objective To investigate the biological characteristics of spindle and kinetochore-associated complex 1 (SKA1) in renal clear cell carcinoma and its correlation with clinical features. Methods First, sequencing data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database were analyzed to determine the differential expression of SKA1 across pan-cancer. Second, clinical postoperative samples of renal clear cell carcinoma, including tumor tissues and adjacent non-tumor tissues, were collected, and quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to measure the mRNA and protein expression levels of SKA1. Finally, ROC curves, Kaplan-Meier survival curves, and Cox proportional hazards regression analysis were applied to evaluate the diagnostic efficacy and prognostic value of SKA1 in renal clear cell carcinoma, and a protein-protein interaction network of SKA1 was constructed for functional enrichment analysis. Results Upregulated SKA1 exhibited significant oncogenic effects at the pan-cancer level. Experimental validation using clinical samples revealed that both the protein and mRNA expression levels of SKA1 were significantly higher in renal clear cell carcinoma tissues compared with adjacent non-tumor tissues (P<0.01). Upregulation of SKA1 promoted malignant progression of renal clear cell carcinoma and was associated with aggressive clinicopathological features. protein-protein interaction and functional enrichment analyses suggested that SKA1 may exert oncogenic effects by accelerating cell cycle and proliferation-related processes through the regulation of mitosis. Conclusion SKA1 is significantly overexpressed in renal clear cell carcinoma. As an oncogene, SKA1 is closely correlated with poor prognosis of renal clear cell carcinoma and shows favorable diagnostic efficacy.

关键词

纺锤体-着丝粒相关复合物亚基1(SKA1) / 肾透明细胞癌 / 表达差异 / 预后

Key words

Spindle and kinetochore-associated complex 1(SKA1) / Renal clear cell carcinoma / Differences in expression / Prognosis

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基金资助

^*中央高水平中医医院临床科研费资助(DZMG-LJRC0009);北京中医药薪火传承“3+3”工程(No.405120602)