The effect of the seleno-L-methionin, sodium selenite and cadmium chloride on telomerase activity of chick embryo neural tube cells

Abstract

Background: Cervical Cancer (CC) is the fourth most common cancer in women worldwide. Potential biomarkers in cancer can be identified by considering the changes in tumoral glycolysis. In this work, we investigated whether the expression of some glycolytic enzymes is associated with the overall and disease-free survival of patients with CC. Methods: We analyzed the expression of 14 genes related with glycolysis (SLC2A1, ADPGK, ALDOA, EDARADD, ENO1, GAPDH, GPI, HK2, LDHA, PFKP, PGK1, PKM, TPI1P1, SLC9A1) in 67 CC, 10 high-grade cervical intraepithelial neoplasia (HG-CIN) and 17 healthy cervical epitheliums (HCE), as controls, with the Human Gene 1.0 ST Microarray (HG 1.0 ST). Validation of gene expression of LDHA and PFKP was performed by qRT-PCR and immunohistochemistry. The expression of LDHA and PFKP was correlated with 5-year survival of CC patients by the Kaplan-Meier method, and FIGO staging and the gene expression were included as covariates in a Cox proportional hazard model. Results: The amount of the mRNA transcribed from the 14 glycolytic genes was higher in CC tumors than in HG-CIN and HCE. Overexpression of genes TPI1P1, LDHA, PFKP, GAPDH, GPI, PGK1 was associated with poor survival, but only the overexpression of LDHA and PFKP genes was independent of the FIGO stage. The qRT-PCR assays confirmed that the overexpression of LDHA and PFKP were associated with poor overall survival (LDHA p= 0.004, PFKP p ¼ 0.0043, Long-rang test) and diseasefree survival (LDHA p ¼ 0.001, PFKP p = 0.013, Long-rang test) in an independent fashion of the FIGO stage (LDHA p ¼ 0.050, PFKP p ¼ 0.029, Cox proportionalhazards regression). Interestingly, only the protein encoded by LDHA gene, analyzed by immunohistochemistry, showed a significant higher expression in recurrent than in non-recurrent tumors. Conclusions: Our results indicate that the expression of LDHA and PFKP at the mRNA and protein levels may be good biomarkers for overall and disease-free survival, independent of FIGO clinical stage, and could be potential therapeutic target for CC. Legal entity responsible for the study: Conacyt, Mexico. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.