Gene expression levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence and risk of death in cervical cancer

Abstract

AbstractBackgroundUp to 74% of patients with cervical cancer (CC) may experience recurrence after their treatment, and most of them are identified late when only the clinical parameters are used, which decreases their chances of recovery. Molecular markers can improve the prediction of clinical outcome and identify therapeutic targets in CC. Glycolysis is altered in 70% of CCs, so it could be a metabolic pathway in which molecular markers associated with the aggressiveness of CC can be identified.MethodsThe expression of 14 glycolytic genes was analyzed in 118 CC samples by microarrays, and only LDHA and PFKP were validated by qRT–PCR (n=58) and in second and third replicates by Western blotting (n=69) and immunohistochemistry (n=18).ResultsLDHA and PFKP were associated with poor overall survival [OS: LDHA HR=3.0 (95% CI= 1.1-8.2); p=2.9 × 10-2; PFKP HR=3.4 (95% CI= 1.1-10.5); p= 3.5 × 10-2] and disease-free survival [DFS: LDHA HR=2.7 (95% CI= 1.6-6.3); p=2.6 × 10-2] independent of FIGO clinical stage. The risk of death was greater when both biomarkers were overexpressed than when using only FIGO stage [HR =7 (95% CI 1.6-31.1, p=1.0 × 10-2) versus HR=8.1 (95% CI=2.6-26.1; p=4.3 × 10-4)] and increased exponentially as the expression of LDHA and PFKP increased.ConclusionsLDHA and PFKP at the mRNA and protein levels were associated with poor overall survival, disease-free survival and increased risk of death of patients with CC regardless of FIGO stage. The measurement of expression of these two markers could be very useful to evaluate the clinical evolution and the risk of death from CC and to make better therapeutic decisions at the beginning of treatment.