The role of CPT1A as a biomarker of breast cancer progression: a bioinformatic approach

Breast cancer is the commonest malignancy of women and with its incidence on the rise, the need to identify new targets for treatment is imperative. There is a growing interest in the role of lipid metabolism in cancer. Carnitine palmitoyl-transferase-1 (CPT-1); the rate limiting step in fatty acid oxidation, has been shown to be overexpressed in a range of tumours. There are three isoforms of CPT-1; A, B and C. It is CPT-1A that has been shown to be the predominant isoform which is overexpressed in breast cancer. We performed a bioinformatic analysis using readily available online platforms to establish the prognostic and predictive effects related to CPT-1A expression. These include the KM plotter, the Human Protein Atlas, the cBioPortal, the G2O, the MethSurvand the ROC plotter. A Network analysis was performed using the Oncomine platform and signalling pathways constituting the cancer hallmarks, including immune regulation as utilised by NanoString. The epigenetic pathways were obtained from the EpiFactor website. Spearman correlations (r) to determine the relationship between CPT-1A and the immune response were obtained using the TISIDB portal. Overexpression of CPT-1A largely confers a worse prognosis and CPT-1A progressively recruits a range of pathways as breast cancer progresses. CPT-1A's interactions with cancer pathways is far wider than previously realised and includes associations with epigenetic regulation and immune evasion pathways, as well as wild-type moderate to high penetrant genes involved in hereditary breast cancer. Although CPT-1A genomic alterations are detected in 9% of breast carcinomas, both the alteration and the metagene associated with it, confers a poor prognosis. CPT-1A expression can be utilised as a biomarker of disease progression and as a potential therapeutic target