The Role of CPT1A as a Biomarker of Breast Cancer Progression – A Bioinformatic Analysis

Background: 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 3 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. Methods 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 tool, the Human Protein Atlas, the cBioPortal tool, the G2O tools, the MethSurv tool, the ROC plotter tool. A Network analysis was performed using the Oncomine platform and the gene concepts for the cancer hallmarks, including immune regulation, were based on the NanoString concepts. The gene concepts for 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. Results Overexpression of CPT-1A largely confers a worse prognosis and that CPT-1A progressively recruits a range of pathways as breast cancer progresses. The scope of this gene’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. CPT-1A genomic alterations are detected in 9% of breast carcinomas and both the alteration and the metagene associated with it, confers a poor prognosis. Conclusions CPT-1A expression can be utilised as a biomarker of disease progression and as a potential therapeutic target.