LDHA and CPT2 association with therapy resistance in prostate cancer

Abstract Background The aerobic glycolysis as energy source in cancer confers a selective advantage for its proliferation and survival. Previous in vitro studies demonstrated that treatment with [C16Pyr][Amp], a potential anti-cancer drug in prostate, decreased the transcript levels of LDHA and CPT2, both involved in metabolic plasticity. In fact, LDHA and CPT2 were reported to be overexpressed in cancer, with association with poor prognosis and resistance to chemo- and radiotherapy. Since LDHA and CPT2 can be potential therapy resistance biomarkers, the aim of this work was to assess LDHA and CPT2 expression using PCa tissues. Methods LDHA and CPT2 expression was evaluated by immunohistochemistry in 57 PCa tissues, 24 from patients that developed resistance to hormonal therapy and 33 without therapy resistance. For both proteins, percentage of positive tumor cells, intensity of immunostaining, and immunoexpression pattern was determined by a blinded manner. Comparisons between therapy variables and protein expression were assessed using the Chi square test. P < 0.05 indicated a statistically significant difference. Results LDHA expression is significantly associated with therapy resistance (P < 0.001). Moreover, CPT2 pattern’s immunoexpression is also associated with therapy resistant (P < 0.001), being cytoplasmatic expression most frequent in patients that respond to therapy (41%), whereas both nuclear and cytoplasmatic expression is more prevalent in therapy-resistant cases (48%). Conclusions LDHA overexpression is significantly associated with therapy resistance in PCa cases, while CPT2 cell expression distribution might be a predictive marker.