The mRNA Expression Signature and Prognostic Analysis of Multiple Fatty Acid Metabolic Enzymes in Clear Cell Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is a metabolic disease, and accumulating evidences indicate significant alterations in the cellular metabolism, especial aerobic glycolysis and glutamine metabolism, in RCC. However, fatty acid (FA) metabolism has received less attention, and the mRNA expression pattern and prognostic role of FA metabolic enzymes in clear cell RCC (ccRCC) have not been carefully examined. In the current study, we first investigated the mRNA expression profiles of multiple FA metabolic enzymes, i.e., ACLY, ACC, FASN, SCD, CPT1A, HADHA, HADHB, and ACAT1, in 42 ccRCC and 33 normal kidney tissues using the Oncomine database, validated their mRNA expression profiles using GEPIA resource, then evaluated and validated the prognostic significance of these metabolic enzymes in 530 ccRCC patients using Kaplan-Meier plotter and GEPIA analyses respectively. The Oncomine and GEPIA confirmed higher ACLY, SCD, and lower ACAT1 mRNA expression in ccRCC than normal tissues (P<0.05). And further prognostic analysis displayed that overexpression of the some FA anabolic enzymes (FASN) was correlated to poor overall survival (OS), while overexpression of the FA catabolic enzymes (CPT1A, HADHA, HADHB, and ACAT1) was correlated to favorable OS in ccRCC patients. In conclusion, multiple FA metabolic enzymes, such as FASN, HADHA, and ACAT1, were potential prognostic markers of ccRCC, which implied alterations in FA metabolism might be involved in ccRCC tumorigenesis and progression.

Journal of Cancer. 2019 Oct 21*** epublish ***

Zuohui Zhao, Yueran Liu, Qiang Liu, Fei Wu, Xiaoli Liu, Hongyi Qu, Yijiao Yuan, Juntao Ge, Yue Xu, Hao Wang

Department of Pediatric Surgery, The First Affiliated Hospital of Shandong First Medical University, Jingshi Road, No. 16766, Jinan, Shandong 250014, China., Department of Operatology, School of Medicine, Shandong University, Wenhuaxi Road, No. 44, Jinan, Shandong 250012, China., Laboratory of Microvascular Medicine, Medical Research Center, The First Affiliated Hospital of Shandong First Medical University, Jingshi Road, No. 16766, Jinan, Shandong 250014, China., Department of Urology, The First Affiliated Hospital of Shandong First Medical University, Jingshi Road, No. 16766, Jinan, Shandong 250014, China., Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jiyan Road, No. 440, Jinan, Shandong 250117, China.