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Identification of SPOP related metabolic pathways in prostate cancer
Min Yan1,2,3, Huan Qi1, Jia Li2,3
1Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Abstract:
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.
Insights
SPOP mutations in prostate cancer are linked to significant metabolic changes. This study reveals altered pathways in fatty acid and TCA cycles, offering new insights into prostate cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Metabolomics
Background:
- Speckle-type POZ protein (SPOP) is frequently mutated in prostate cancer (PCa).
- The role of SPOP mutations in PCa metabolic reprogramming is largely unknown.
- SPOP functions as a cullin-based E3 ubiquitin ligase.
Purpose of the Study:
- To investigate the impact of SPOP mutations on metabolic reprogramming in prostate cancer.
- To identify specific metabolic pathways altered in SPOP-mutated PCa.
- To correlate SPOP mutations with changes in gene expression and metabolic profiles.
Main Methods:
- Integrated analysis of transcriptomics, metabolomics, and lipidomics in matched PCa tumor (PCT) and adjacent non-tumor (ANT) tissues.
- Correlation analysis of SPOP mutations with altered metabolic pathways.
- Utilized cBioportal for data validation.
Main Results:
- SPOP mutations, found in 16.7% of cases (11/66), occurred at conserved MATH domain residues.
- Upregulation of the tricarboxylic acid (TCA) cycle, fatty acid metabolism, and glycerophospholipid metabolism was observed in SPOP-mutated PCT tissues.
- FH, ELOVL2, and ACADL genes were identified as potentially involved in SPOP-mutation-related metabolic alterations.
Conclusions:
- SPOP mutations are associated with significant metabolic reprogramming in prostate cancer.
- Altered TCA cycle, fatty acid, and glycerophospholipid metabolism are key features of SPOP-mutated PCa.
- This study provides novel insights into the interplay between SPOP mutations and metabolic pathways in PCa pathogenesis.
