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.
Journal of Cancer. 2019 May 22*** epublish ***
Yongwen Luo, Liang Chen, Gang Wang, Guofeng Qian, Xuefeng Liu, Yu Xiao, Xinghuan Wang, Kaiyu Qian
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China., Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China., Department of Endocrinology, the First Affiliated Hospital of Zhejiang University, Hangzhou, China., Department of Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School, Washington DC, USA.