ENO1 as a biomarker of breast cancer progression and metastasis – a bioinformatic approach

Abstract

AbstractBackgroundMetabolic reprogramming is one of the hallmarks of cancer cells and many key metabolic enzymes are dysregulated. In breast cancer (BC), the commonest malignancy of women, several metabolic enzymes are overexpressed and/or overactivated. One of these is Enolase 1 (ENO1) an enzyme that catalyses glycolysis but is also involved in the regulation of multiple signalling pathways. ENO1 overexpression in BC has been linked to worse tumour prognosis and metastasis, rendering it a promising biomarker of disease progression and a potential therapeutic target.MethodsUtilising available online platforms such as the KM-plotter, the ROC-plotter, the cBioPortal, the G-2-O, the MethSurvand, we performed a bioinformatic analysis to establish the prognostic and predictive effects related to ENO1 expression in breast cancer. A Network analysis was also performed using the Oncomine platform and signalling and epigenetic pathways including immune regulation constituting the hallmarks of cancer were explored. The relationship between ENO1 and the immune response was also obtained from the TISIDB portal and Spearman’s rho (r) was used to determine their correlation.ResultsENO1 is overexpressed in all the analysed Oncomine, epigenetic and immune pathways in triple-negative, but not in hormone receptor-positive BCs. In HER2-positive BCs, ENO1 expression showed a mixed profile. Similarly, analysis on disease progression and histological types showed ENO1 overexpression in ductalin situand invasive carcinoma, high grade tumours followed by advanced and/or metastasis and was linked to worse survival (death by 5 years). High ENO1 expression was also associated with relapse-free (RFS), distant metastasis-free (DMFS) and overall survival (OS) as analysed by the KM-plot software, irrespectively of treatment and was also related to basal subtype and to a lesser extend to HER2 and luminal B subtypes. ENO1 was underexpressed in the less invasive and with better prognosis subtypes.ConclusionsOverexpression of ENO1 largely confers a worse prognosis in breast cancer and recruits a range of signalling pathways during disease progression. ENO1 expression can be utilised as a biomarker of disease progression and as a potential therapeutic target, particularly in triple-negative and invasive breast carcinomas (NST).