PROGNOSTIC VALUE OF γH2AX IN PRE-CHEMOTHERAPY PERIPHERAL BLOOD LEUKOCYTES (PBL) FROM CANCER PATIENTS TREATED WITH PLATINUM ANALOGS

MAYRA L. SOTTILE; GARCIA MARÍA BELÉN; REYNALDO J. FLORES LEYVA; ANALÍA REDONDO; JORGE IBARRA; LAURA M. VARGAS ROIG; SILVINA B. NADIN

Mendoza

Congreso; XXXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2018

Sociedad de Biología de Cuyo

Cisplatin (cisPt) constitute a widely used chemotherapeutic drug for the treatment of solid tumors. The mechanism of action is based on the formation of DNA-interstrand and -intrastrand crosslinks, which interfere with normal DNA function. H2AX phosphorylation (γH2AX) facilitates the recruitment of DNA damage repair proteins to the chromatin surrounding DNA lesion. The expression of γH2AX has been proposed as a tool to monitor DNA damage and repair in translational cancer research. The aim of our work was to determine the prognostic and predictive value of γH2AX in peripheral blood leukocytes (PBL) from cancer patients treated with cisPt. We isolated PBL from 6 healthy persons and 32 cancer patients (mean follow-up 13 months) before chemotherapy. PBL were in vitro exposed to cisPt (200 µM, 1 h) and harvested at T0 (immediately after cisPt), T24 and T48 (24 and 48 h after recovery, respectively). γH2AX expression was evaluated by immunocytochemistry. At basal conditions, there were no statistically differences in the number of γH2AX foci/nucleus and in the percentage of γH2AX-positive cells between healthy subjects and cancer patients. PBL from healthy individuals and patients showed a significant increase (P˂0.05) in the number of γH2AX foci/nucleus 24 h after cisPt. However, γH2AX foci/nucleus decreased after 48 h of recovery in PBL from healthy subjects, but they were not modified in PBL from cancer patients. Statistically significant differences between patients with complete clinical response to chemotherapy and those with partial response, stable or progressive disease were not found for the number of γH2AX foci/nucleus. A high number of γH2AX foci/nucleus in cancer patients was associated with better overall survival (P˂0.05). Our preliminary findings indicate that detection of number of γH2AX foci/nucleus in pre-chemotherapy PBL from cancer patients may be a useful prognostic marker for cancer patients treated with platinum-based chemotherapy. Trabajo con MENCIÓN ESPECIAL