Integration of lipidomics and transcriptomics reveals reprogramming of the lipid metabolism and composition in clear cell renal cell carcinoma

Giuseppe Lucarelli, Matteo Ferro, Davide Loizzo, Cristina Bianchi, Daniela Terracciano, Francesco Cantiello, Lauren N. Bell, Stefano Battaglia, Camillo Porta, Angela Gernone, Roberto A. Perego, Eugenio Maiorano, Ottavio de Cobelli, Giuseppe Castellano, Leonardo Vincenti, Pasquale Ditonno, Michele Battaglia

Research output: Contribution to journalArticlepeer-review

Abstract

Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase(SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance.

Original languageEnglish
Article number509
Pages (from-to)1-18
Number of pages18
JournalMetabolites
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Cholesterol
  • Lipidomics
  • Lipids
  • Renal cell carcinoma
  • SCD1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology

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