Study of HV1 channel expression in clinical samples of breast cancer through clinical databases analysis

VENTURA, CLARA; ENRIQUE, NICOLÁS JORGE; MARTÍN, PEDRO; FELICE, JUAN IGNACIO; ISSOURIBEHERE, DIEGO; MILESI, VERÓNICA

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

Sociedad Argentina de Investigación Clínica (SAIC), Sociedad Argentina de Inmunología (SAI) y Sociedad Argentina de Fisiología (SAFIS)

Metabolic reprogramming, an emerging hallmark ofcancer, conduces to a large production of acidic substances requiring the overexpression of H+ extrusion cell structures. We have previouslyreported that proton channel (HVCN1) has a key role in this process in breastcancer cell lines and Jurkat T cells, and its inhibition induces apoptosis. Theaim of this work was to analyze the HVCN1 channel expression (mRNA) in clinicalsamples of normal and neoplastic human mammary tissue and its correlation withkey metabolic reprogramming-related gene increased in several types of cancers(Tanner et al., 2018, Cell Systems 7, 1?14). To this end, GEPIA and cBioPortal databases information was used. Theanalysis of GEPIA database showed that not significant differences of HVCN1expression (Transcripts per Millon) appears between normal (N=291) andpathological (N=1085) mammary tissues. However, we observed different HVCN1expression levels within tumor samples of the Breast Cancer ETABRIC, Nature2012 & Nat Commun 2016 study. Selecting samples in which HVCN1 mRNA levelwas major to one standard deviation of the median (high Hv1 group; N=250) andcompared this group with the rest of the samples (control group; N=1653), weobserved that the high Hv1 group contains a significantly increased number oftriple negative and claudin-low samples respect to the control group(Chi-quadrate test, p<10-10), and found that 4530 genes are significantlyenriched (Student test) in the high Hv1 group, including metabolic reprogramingrelated genes such as GLUT3 (p=3.07e-19), GLUT5 (p=4.66e-25), PFKP (p=9.44 6e-9) and PFKL (p=2.04e-3),which are indicated as key genes of glycolytic flux. Altogether, our resultsdemonstrated that HV1 expression could be associated invasivesubtypes and glycolytic phenotype, pointing out the role of this channel inbreast cancer.