This study attempts to evaluate the prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC) by means of publicly available data from The Cancer Genome Atlas (TCGA). Clinical pathologic features and PHYH expression were downloaded from the TCGA database and relationships between them were analyzed by univariate and multivariate Cox regression analyses. Gene Set Enrichment Analysis (GSEA) and gene-gene interactions were also performed between tissues with different PHYH expression levels. PHYH expression levels were significantly lower in patient with ccRCC compared with normal tissues (p = 1.156e-19). Kaplan-Meier survival analysis showed that high expression of PHYH had a better prognosis than low expression (p = 9e-05). Moreover, PHYH expression was also significantly associated with high grade (G2-4, p = 0.025), high stage (StageIII & IV, p = 5.604e-05), and high level of stage_T (T3-4, p = 4.373e-05). Univariate and multivariate Cox regression analyses indicated that PHYH could be acted as an independent prognostic factor (p < 0.05). Nomogram including clinical pathologic features and PHYH expression were also provided. GSEA revealed that butanoate metabolism, histidine metabolism, propanoate metabolism, pyruvate metabolism, tryptophan metabolism, PPAR signalling pathway, and renin-angiotensin system were differentially enriched in PHYH high-expression phenotype. ICGC database was utilized to verify the expression level and survival benefit of PHYH (both p < 0.05). We suspect that elevated PHYH expression may be served as a potential prognostic molecular marker of better survival in ccRCC. Besides, alpha-oxidation was closely regulated by PHYH, and PPAR signalling, pyruvate metabolism, butanoate metabolism, and RAS might be the key pathways regulated by PHYH in CCRC.
European journal of medical research. 2021 Jan 19*** epublish ***
Qiu Zhengqi, Guo Zezhi, Jiang Lei, Qiu He, Pan Jinyao, Ao Ying
Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Carson International Cancer Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, China. ., Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Carson International Cancer Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, China.