PPARα gene is a diagnostic and prognostic biomarker in clear cell renal cell carcinoma by integrated bioinformatics analysis

Genetic alterations in lipid metabolism genes are correlated with progression and poor prognosis of Clear cell renal cell carcinoma (ccRCC). PPAR alpha play a critical role in lipid metabolism. This study aimed to identify that PPAR alpha 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 PPAR alpha gene in various tumor types, qRT-PCR and immunohistochemical staining experiments were utilized for validation. Next, ccRCC data were obtained from TCGA. Correlation between PPAR alpha expression levels and patients' clinicopathological characteristics was assessed, and the clinically diagnosis and prognostic value of PPAR alpha were explored in ccRCC. According to the gene set enrichment analysis (GSEA) analysis, PPAR alpha gene associated biological pathways were identified. PPAR alpha has prognostic significance only in ccRCC tumors. Expression of PPAR alpha was associated with ccRCC stages. PPAR alpha was significantly down-regulated in ccRCC and associated with survival. Gender, tumor dimension, grade and stage showed a significant relevance with PPAR alpha expression. Lower PPAR alpha expression revealed significantly poorer survival and progression compared with higher PPAR alpha expression. Adjusted by other clinical risk factors, PPAR alpha remained an independent prognostic factor. Moreover, Low PPAR alpha expression was a potential diagnostic biomarker of ccRCC. A nomogram was constructed based on PPAR alpha expression and other clinicopathological risk factors, and it performed well in predict patients survival. GSEA analysis showed that PPAR alpha gene associated biological pathways were enriched in mTOR pathway, AKT pathway, IGF1-mTOR pathway and Wnt signaling pathways. In conclusion, PPAR alpha expression was decreased in ccRCC tumors. Lower expression of PPAR alpha is closely correlated with poorer survival. It can be used as a clinically diagnosis and prognostic biomarker in ccRCC.