Abstract 1518: Gene expression profile and gender differences related with immune processes in solid tumors
Authors: Araujo Jhajaira M. , Raez Luis E. , Rolfo Christian D. , Schwarz Luis J. , Infante-Huaytalla Ulises , Paez Kevin J. , García Luis R. , Alvarado Hober , Ramos Fany P. , Delgado-Espinoza Sheyla S. , Cardenas-Farfan Jhon B. , Barboza-Meca Joshuan J. , Caballero-Alvarado Jose , Pinto Joseph A. 
Published: August 2019

Abstract
Background: We have described before differences in gene expression profile (GEP) of immune gene-sets between genders in non-small cell lung cancers (NSCLC). On the other hand, there are reports mentioning the benefit of immune checkpoint inhibitors (ICI) could be influenced by gender, suggesting differences in immune processes (IP). We decided to evaluate if there are gender-specific differences in solid tumors including melanoma, gastric adenocarcinomas (GAC), head and neck cancer (HNC) and clear renal cell carcinoma (CCRCC).
Methods: GEO (https://www.ncbi.nlm.nih.gov/geo/) datasets were retrieved and analyzed for melanoma, GAC, HNC and CCRCC that contained GEP across Affymetrix and Illumina Microarrays of primary tumors. Datasets were manually verified and cases without gender information or non-tumoral tissue were excluded. Cell lines were not considered in our analysis. Data was pre-processed and gene-set enrichment analysis (GSEA) was conducted individually in the datasets GSE6791, GSE30784, GSE78060, GSE34105, GSE65858 (HNC); GSE73731, GSE36895, GSE11904, GSE40435 (CCRCC); GSE26899, GSE26901 (GAC) and GSE15605 (melanoma). Immune process (IP) grouped by gene ontology and identified with a p-value&lt;0.05 and a FDR&lt;25% were considered enriched.
Results: The number of IP enriched in women was higher than men in HNC (306 IP), GAC (297 IP) followed by melanoma (128 IP) and CCRCC (30 IP). Pathways significantly enriched in women in the four evaluated malignancies were: activation of immune response, activation of innate immune response, antigen receptor mediated signaling pathway, immune response regulating cell surface receptor signaling pathway, positive regulation of innate immune response, regulation of innate immune response and T cell receptor signaling pathway. In contrast to other cancers, only CCRCC showed enrichment of immune gene sets in males.
Conclusions: We find strong patterns of GEP of immune genes in tumors from female patients, suggesting gender-specific patterns of response to ICI. This pool of immune genes differentially expressed could be used as candidate biomarkers for prediction of response to immunotherapy.
Citation Format: Jhajaira M. Araujo, Luis E. Raez, Christian D. Rolfo, Luis J. Schwarz, Ulises Infante-Huaytalla, Kevin J. Paez, Luis R. García, Hober Alvarado, Fany P. Ramos, Sheyla S. Delgado-Espinoza, Jhon B. Cardenas-Farfan, Joshuan J. Barboza-Meca, Jose Caballero-Alvarado, Joseph A. Pinto. Gene expression profile and gender differences related with immune processes in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1518.