Examining the Role of the Inhibitor of Apoptosis birc6 in Lung Adenocarcinoma

GÓMEZ BERGNA, SANTIAGO MANUEL; ROMANOWSKI, VICTOR; AMORÓS MORALES, LESLIE; PIDRE, MATÍAS LUIS; MARCHESINI, ABRIL; GOTTARDO, MARÍA FLORENCIA

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

Women in Bioinformatics and Data Science LA

Inhibitors of apoptosis (IAP) have been shown to play a central role in the development andaggressiveness of different tumors. Tumors resistant to conventional treatments, such aschemo and radio therapy, could take advantage of pathways such as the DNA damageresponse (DDR). The aim of this work was to characterize the role of the IAP family in lungadenocarcinoma (LAC), with the intention of proposing a new therapeutic target.Two TCGA transcriptomic databases were analyzed and seven IAP were queried (cBioPortaland Xena platform). Our results demonstrated that at least two (BIRC5 and BIRC6) of theseven IAP have a higher expression in tumor compared to normal tissue (ANOVA). Also, ourresults showed that LAC patients with a higher BIRC6 copy number was associated withresistance to radiotherapy and tumor recurrence (χ2).In order to further characterize the role of BIRC6 in LAC, we run a Gene Ontology (GO) andPathway Enrichment Analysis using the Xena platform´s differential expression tool. Wecompared the results with those obtained for BIRC5, the best known member of the IAP family,XIAP and NAIP. These results show that BIRC6 is involved in DDR, specifically via the ATMand ATR pathways.To go deeper into this findings, we analyzed the expression levels of some the genes involvedin the ATM and ATR pathways. As result we observed a higher expression in most of thegenes involved in both pathways, in tumor samples that present a high expression of BIRC6.On the other hand, samples with high BIRC5 expression, only most of the ATR genes wereup-regulated. (Welch's t-test). BIRC6 overexpression is known to be associated with poor prognosis in different tumors. Thisfact, together with our results are encouraging and open the way to future preclinical studies,postulating BIRC6 as a promising therapeutic target.