Identification of SPOP related metabolic pathways in prostate cancer
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Min Yan1,2,3, Huan Qi1, Jia Li2,3, Guozhu Ye2,3, Yaping Shao2,3, Tongming Li1, Jing Liu1, Hai-Long Piao1,3 and Guowang Xu2,3
1Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
2CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
3University of Chinese Academy of Sciences, Beijing 100049, China
Guowang Xu, email: [email protected]
Hai-Long Piao, email: [email protected]
Keywords: SPOP, metabolism
Received: May 04, 2017 Accepted: September 18, 2017 Published: October 03, 2017
Speckle-type POZ protein (SPOP), as a cullin-based E3 ubiquitin ligase, has been identified as one of the most frequently mutated genes in prostate cancer (PCa). However, whether SPOP mutations contribute to metabolic reprogramming in PCa remains unknown. Here, integrated studies of transcriptomics and metabolomics as well as lipidomics were performed in matched PCa tumor (PCT) and adjacent non-tumor (ANT) tissues, followed by correlation analysis of SPOP mutations with altered metabolic pathways in SPOP-mutated PCa patients. Interestingly, transcriptomics profiling showed that all SPOP mutations (with 16.7% frequency, 11/66) occurred at the conserved residues in the substrate binding domain of meprin and TRAF homology (MATH). The results of integrated analysis indicated that three metabolic pathways, including tricarboxylic acid (TCA) cycle, fatty acid metabolism and glycerophospholipid metabolism, exhibited obvious upregulation in SPOP-mutated PCT tissues. Furthermore, both correlation analyses based on integrated data and cBioportal revealed that FH, ELOVL2 and ACADL genes might be involved in SPOP-mutation-related upregulation of these metabolic pathways. Taken together, our study provided new insights in understanding the relationship between metabolic pathways and SPOP mutations in PCa.
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