Enrichment analysis associated to vav3 expression in melanoma

ÁVILA, AYLEN; MENACHO-MÁRQUEZ, MAURICIO; ANSELMINO, LUCIANO

Congreso; Reunión Conjunta SAIC. SAI. AAFE. NANOMED-AR; 2021

Skin cutaneous melanoma (SKCM) is the most severe form of skincancer, originated from the malignant transformation and prolifera-tion of melanocytes.According to the existing paradigm for the Rho GEFs (guanine nu-cleotide exchange factors), the Vav subfamily is commonly assumedto be involved in protumorigenic pathways in tumor cells. Interest-ingly, we have recently proposed an unexpected tumor suppressorrole for Vav3 in melanoma. In this tumor type, Vav proteins playimportant roles during development, tumor growth and metastasis.In this work, we explore molecular functions associated to Vav3 inmelanoma by bioinformatics. First, by survival analysis tools andusing human patient databases, we found that Vav3 expression cor-related with patient survival (p<0.001). To explore pathways asso-ciated to Vav3 expression levels we created two groups of patientswith low and high levels of Vav3. The clinical and molecular infor-mation was obtained from the dataset Skin Cancer Melanoma fromThe Cancer Genome Atlas (SKCM-TCGA). We used TCGABiolinksand edgeR packages in R, to identify differentially expressed genes(DEGs; |logFC|>1 and FDR<0.01).The molecular function of this group of DEGs was obtained usingthe Panther Classification System of the Gene Ontology Consor-tium. Of the 579 genes categorized by molecular function, 29% ofthem were associated to “binding function”, especially “protein bind-ing” (51.2%), and 18.5% to “catalytic function”, especially “hydrolaseactivity” (57.9%). With this set of DEGs we performed a Gene SetFunctional Enrichment Analysis (GSEA). As expected, we observedan enrichment for the Rho GTPase pathway in patients with highVav3 expression, and pathways related to both innate and adaptiveimmune system (FDR<0.25), such as the interleukin-2 and gammainterferon pathways.Our preliminary data suggest that Vav3 could be associated to atranscriptional program that controls immune responses in melano-ma.