In silico approach to explore the role of the Rho GEF VAV3 in melanoma

ÁVILA, AYLEN; ANSELMINO, LUICANO; CESATTI LALUCE, NAHUEL; MAMBERTO, MACARENA; BUSTELO, XOSÉ; MENACHO-MÁRQUEZ, MAURICIO

Buenos Aires

Congreso; WORLD SKIN CANCER CONGRESS; 2022

GEFs (Guanosine nucleotide Exchange Factors) promote the transition of small GTPases from inactive to active states. RHO GEFs, as VAV proteins, play essential roles in different cellular processes and in human diseases. Although RHO GEFs have traditionally been considered to exert proactive functions in cancer, we have observed an unexpected tumor-suppressor role for VAV3 in melanoma.In this work we aim to explore by bioinformatic approaches the putative suppressor-related functions of VAV3 in the context of melanoma, the most severe form of skin cancer. To address this, we employed the TCGABiolinks package to download gene expression data queried from skin cutaneous melanoma patients from the Cancer Genome Atlas (TCGA). First, a survival plot was performed using the Kaplan-Meier estimator, with the SurvMineR package and the cutoff value for high and low VAV3 expression was obtained. To identify differentially expressed genes (DEGs) between the groups we use the edgeR package to perform an “exact test” based on the quantile-adjusted conditional maximum likelihood method. DEGs were considered for |FC|>1.5 and FDR0.05). However, we observed an association between higher probability of survival and high VAV3 expression levels (p