Examining the role of the inhibitor of apoptosis BIRC6 in lung adenocarcinoma

MARCHESINI ABRIL; GÓMEZ BERGNA SANTIAGO MANUEL; AMORÓS MORALES LESLIE C.; GOTTARDO MARÍA FLORENCIA; ROMANOWSKI VÍCTOR; PIDRE MATIAS LUIS

Congreso; 2nd Women in Bioinformatics & Data Science LA Conference; 2021

Inhibitors of apoptosis (IAP) have been shown to play a central role in the developmentand aggressiveness of different tumors. Tumors resistant to conventional treatments,such as chemo and radio therapy, could take advantage of pathways such as the DNAdamage response (DDR). The aim of this work was to characterize the role of the IAPfamily in lung adenocarcinoma (LAC), with the intention of proposing a new therapeutictarget. Two TCGA transcriptomic databases were analyzed and seven IAP were queried(cBioPortal and Xena platform). Our results demonstrated that at least two (BIRC5 andBIRC6) of the seven IAP have a higher expression in tumor compared to normal tissue(ANOVA). Also, our results showed that LAC patients with a higher BIRC6 copy numberwas associated with resistance to radiotherapy and tumor recurrence (χ2). In order tofurther characterize the role of BIRC6 in LAC, we run a Gene Ontology (GO) andPathway Enrichment Analysis using the Xena platform ́s differential expression tool.We compared the results with those obtained for BIRC5, the best known member ofthe IAP family, XIAP and NAIP. These results show that BIRC6 is involved in DDR,specifically via the ATM and ATR pathways. To go deeper into these findings, weanalyzed the expression levels of some the genes involved in the ATM and ATRpathways. As result we observed a higher expression in most of the genes involved inboth pathways, in tumor samples that present a high expression of BIRC6. On theother hand, samples with high BIRC5 expression, only most of the ATR genes were up-regulated. (Welch's t-test). BIRC6 overexpression is known to be associated with poor prognosis in different tumors. This fact, together with our results are encouraging andopen the way to future preclinical studies, postulating BIRC6 as a promisingtherapeutic target.