THE INHIBITOR OF APOPTOSIS BIRC6 AND ITS ROLE IN NON-SMALL CELL LUNG CANCER

ABRIL MARCHESINI; GÓMEZ BERGNA, SANTIAGO M.; AMORÓS MORALES, LESLIE C.; GOTTARDO, M FLORENCIA; VICTOR ROMANOWSKI; PIDRE, MATIAS L.

Rosario

Congreso; XIII Argentine Congress of Bioinformatics and Computational Biology (XIII CAB2C), XIII International Conference of the Iberoamerican Society of Bioinformatics (XIII SoIBio) and III Annual Meeting of the Ibero-American Artificial Intelligence Network for B; 2023

rgentine Association of Bioinformatics and Computational Biology (A2B2C) together with the Iberoamerican Society of Bioinformatics (SoIBio) and the Ibero-American Artificial Intelligence Network (RiaBio)

BACKGROUND:Lung cancer is the main cause of cancer-related deaths worldwide, comprising two main morphological groups: small cell lung cancer (SCLC,accounting for 15% of cases) and non-small cell lung cancer (NSCLC, representing 85% of cases). Inhibitors of apoptosis (IAP) have beenidentified as central players in the development and aggressiveness of various tumors. Tumors resistant to conventional treatments, like chemoand radio therapy, could take advantage of pathways such as the DNA damage response (DDR). The aim of this work was to characterize therole of the IAP family in NSCLC, specially in lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC). With the goal to propose anew posible therapeutic target.RESULTS:Two TCGA transcriptomic databases were analyzed and seven IAP were queried (cBioPortal and Xena platform). Our results demonstrated thatat least two (BIRC5 and BIRC6) of the seven IAP have a higher expression in tumor compared to normal tissue in LAC and LSCC (ANOVA).Also, our results showed that LAC patients with a higher BIRC6 copy number seems to be associated with resistance to radiotherapy and tumorrecurrence (χ2). In order to further characterize the role of BIRC6, we run a Gene Ontology (GO) and Pathway Enrichment Analysis using theXena platform ́s differential expression tool. We compared the results with those obtained for BIRC5, XIAP and NAIP. These results show thatBIRC6 could be involved in DDR, specifically via the ATM and ATR pathways. To go deeper into these findings, we analyzed the expression levelsof some the genes involved in the ATM and ATR pathways. As result we observed a higher expression in most of the genes involved in bothpathways, in tumor samples that present a high expression of BIRC6. On the other hand, only most of the ATR genes were up- regulated insamples with high BIRC5 expression (Welch´s t-test).CONCLUSIONS:BIRC6 over expression is known to be associated with poor prognosis in different tumors.This fact, together with our results are encouraging and open the way to future preclinical studies, postulating BIRC6 as a promising therapeutictarget.