Luo Yongwen, Chen Liang, Wang Gang, Qian Guofeng, Liu Xuefeng, Xiao Yu, Wang Xinghuan, Qian Kaiyu
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
J Cancer. 2019 May 22;10(10):2319-2331. doi: 10.7150/jca.29178. eCollection 2019.
Genetic alterations in lipid metabolism genes are correlated with progression and poor prognosis of Clear cell renal cell carcinoma (ccRCC). PPARα play a critical role in lipid metabolism. This study aimed to identify that PPARα is a diagnosis and prognostic biomarker in ccRCC by integrated bioinformatics analysis. UALCAN database was used to explore the differential expression status and prognostic value of PPARα gene in various tumor types, qRT-PCR and immunohistochemical staining experiments were utilized for validation. Next, ccRCC data were obtained from TCGA. Correlation between PPARα expression levels and patients' clinicopathological characteristics was assessed, and the clinically diagnosis and prognostic value of PPARα were explored in ccRCC. According to the gene set enrichment analysis (GSEA) analysis, PPARα gene associated biological pathways were identified. PPARα has prognostic significance only in ccRCC tumors. Expression of PPARα was associated with ccRCC stages. PPARα was significantly down-regulated in ccRCC and associated with survival. Gender, tumor dimension, grade and stage showed a significant relevance with PPARα expression. Lower PPARα expression revealed significantly poorer survival and progression compared with higher PPARα expression. Adjusted by other clinical risk factors, PPARα remained an independent prognostic factor. Moreover, Low PPARα expression was a potential diagnostic biomarker of ccRCC. A nomogram was constructed based on PPARα expression and other clinicopathological risk factors, and it performed well in predict patients survival. GSEA analysis showed that PPARα gene associated biological pathways were enriched in mTOR pathway, AKT pathway, IGF1-mTOR pathway and Wnt signaling pathways. In conclusion, PPARα expression was decreased in ccRCC tumors. Lower expression of PPARα is closely correlated with poorer survival. It can be used as a clinically diagnosis and prognostic biomarker in ccRCC.
脂质代谢基因的遗传改变与透明细胞肾细胞癌(ccRCC)的进展及不良预后相关。过氧化物酶体增殖物激活受体α(PPARα)在脂质代谢中起关键作用。本研究旨在通过综合生物信息学分析确定PPARα是ccRCC的诊断和预后生物标志物。利用UALCAN数据库探索PPARα基因在各种肿瘤类型中的差异表达状态和预后价值,并通过qRT-PCR和免疫组织化学染色实验进行验证。接下来,从TCGA获取ccRCC数据。评估PPARα表达水平与患者临床病理特征之间的相关性,并探讨PPARα在ccRCC中的临床诊断和预后价值。根据基因集富集分析(GSEA)分析,确定与PPARα基因相关的生物学途径。PPARα仅在ccRCC肿瘤中具有预后意义。PPARα的表达与ccRCC分期相关。PPARα在ccRCC中显著下调并与生存相关。性别、肿瘤大小、分级和分期与PPARα表达显示出显著相关性。与较高PPARα表达相比,较低的PPARα表达显示出明显较差的生存和进展情况。经其他临床危险因素校正后,PPARα仍然是一个独立的预后因素。此外,低PPARα表达是ccRCC的潜在诊断生物标志物。基于PPARα表达和其他临床病理危险因素构建了列线图,其在预测患者生存方面表现良好。GSEA分析表明,与PPARα基因相关的生物学途径在mTOR途径、AKT途径、IGF1-mTOR途径和Wnt信号通路中富集。总之,ccRCC肿瘤中PPARα表达降低。较低的PPARα表达与较差的生存密切相关。它可作为ccRCC的临床诊断和预后生物标志物。