Th210 - Regulation of Chemokines Expression Modulated by E6/E7 Oncogenes of HPV Frequently Detected in Cervical Cancer in the Mexican Population

Adriana Aguilar.Lemarroy – Investigador Titular D, División de Inmunologia, Centro de Investigación Biomédica de Occidente; Luis-Felipe Jave-Suarez – Investigador Titular C, División de Inmunologia, Centro de Investigación Biomédica de Occidente; Aribert M. Castro-Amaya

Abstract Text: In Mexico, Cervical Cancer (CC) is ranked second and third in mortality and incidence among pathologies associated with cancer in women. The Human Papillomavirus (HPV) is considered the main risk factor. The E6 and E7 HPV oncogenes have an immunomodulatory effect related to the induction of carcinogenic processes through the uncontrolled expression of different molecules. This study aims to evaluate the expression of chemokines modulated by the E6/E7 oncogenes of frequent HPVs circulating in the Mexican population, to analyze their expression and prognostic value in the development of CC.
The expression of a chemokines panel was analyzed in cell models expressing E6/E7 oncogenes of HPV -16, -18, - 38b, -107, and -122; and in CC-derived cell lines (SiHa, CasKi, HeLa, SW756, and C33a) by next generation sequencing (NGS) and validated by qPCR. Additionally, chemokines expression was determined using the OncoDB tool and a database of 324 cervical squamous cell carcinoma (CESC) biopsies. Finally, survival analyses (Kaplan-Meier) were performed using databases from the repository "The Cancer Genome Atlas Program" (TGCA).
Our results show that CXCL2 and CXCL8 expression increases in the presence of E6/E7 of various HPV genotypes and is overexpressed in CC-derived cell lines and CESC biopsies. This behavior has an unfavorable impact on the survival index in patients with CC. Thus, measuring the expression levels of CXCL2 and CXCL8 could improve the screening techniques for diagnosing/prognosis of cervical lesions.