The Value of CXCL1, CXCL2, CXCL3, and CXCL8 as Potential Prognosis Markers in Cervical Cancer: Evidence of E6/E7 from HPV16 and 18 in Chemokines Regulation

Abstract

Cervical cancer (CC) is a serious global health issue, and it is well-known that HPV infection is the main etiological factor that triggers carcinogenesis. In cancer, chemokine ligands and receptors are involved in tumor cell growth, metastasis, leukocyte infiltration, and angiogenesis; however, information on the role played by E6/E7 of HPV16/18 in the modulation of chemokines is very limited. Therefore, this study aimed to determine whether chemokines are differentially expressed in CC-derived cell lines; if E6/E7 oncoproteins from HPV16 and 18 are capable of mediating chemokine expression, what is the expression profile of chemokines in tissues derived from CC and what is their impact on the overall survival of patients with this pathology? For this purpose, RNA sequencing and real-time PCR were performed on SiHa, HeLa, and C33A tumorigenic cell lines, on the non-tumorigenic HaCaT cells, and the E6/E7 HPV-transduced HaCaT cell models. Furthermore, chemokine expression and survival analysis were executed on 304 CC and 22 normal tissue samples from The Cancer Genome Atlas (TCGA) repository. The results demonstrate that CXCL1, CXCL2, CXCL3, and CXCL8 are regulated by E6/E7 of HPV16 and 18, are overexpressed in CC biopsies, and that their higher expression is related to a worse prognostic survival.

A Retrospective Analysis from Western Romania Comparing the Treatment and Survivability of p16-Positive versus p16-Negative Oropharyngeal Cancer

“…HPV’s carcinogenic potential is driven by its E6 and E7 oncoproteins [ 21 , 23 , 24 , 25 ]. These proteins provoke uncontrolled cell proliferation.…”

Detection of Sialic Acid to Differentiate Cervical Cancer Cell Lines Using a Sambucus nigra Lectin Biosensor

“…The human CC cell lines SiHa, HeLa, and C33A were obtained from the Centro de Investigación Biomédica de Occidente (CIBO) (Guadalajara, México), kindly provided by Ph.D. Adriana Aguilar Lemarroy from the cell bank of the CIBO Immunology Division [27]. Primary fibroblasts were acquired from the Escuela Nacional de Ciencias Biológicas (ENCB-IPN) (Cdmx, México).…”

Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis

“…To discern the molecular process engaged in the viral immune escape, it has been shown that infection with HPV16 inhibits the expression of TLR9 by E6 and E7, resulting in the downregulation of inflammatory cytokines like type-1 IFNs and inhibition of immune responses [ 76 ]. In addition, the study on HPV E6 and E7 in cervical cancer found that they regulate the expression of CXCL1, CXCL2, and CXCL3, as well as CXCL8 chemokines [ 77 ]. Therefore, the immune system targets viral oncogenes expression through OS; however, excessive OS may facilitate HPV DNA integration [ 78 ].…”