Perfil de expressão proteica de G6PD e NADK em carcinoma de células renais como indicador prognóstico

Abstract

Renal cell carcinoma (RCC) is the most lethal urological neoplasm and accounts for approximately 2-3% of all diagnosed cancers. The main histological variants are clear cell (ccRCC), papillary (pRCC) and chromophobe (chRCC). Prognostic factors include TNM classification, Fuhrman grade, and histological subtype. To prevent oxidative stress, during tumor progression, cells activate a complex antioxidant defense system, which depends on the generation of Nicotinamide Adenine Dinucleotide Phosphate (NADPH). NADPH synthesis is regulated by enzymes and metabolic pathways, including Nicotinamide Adenine Dinucleotide Kinase (NADK) and Glucose-6-Phosphate Dehydrogenase (G6PD) in the pentose phosphate pathway. The objective of this study was to investigate the expression of G6PD and NADK associated with prognostic factors and tumor aggressiveness in a RCC cohort from Hospital de Clínicas - UFTM. Protein expressions were analized by immunohistochemistry in 121 cases, associations between expression patterns and clinical and pathological data were investigated through statistical analyses. A higher percentage of labeled cells and a higher G6PD expression score were observed in pRCC and chRCC. Larger tumors had a higher percentage of positive cells, and, in the ccRCC group, the highest G6PD expression score also indicated more extensive tumors. A higher percentage of labeled cells and G6PD expression score were also associated with higher Fuhrman grades. The presence of tumor necrosis was associated with the G6PD expression score only in the ccRCC group. Regarding the NADK enzyme, all cases of pRCC and chRCC showed more than 50% of labeled cells, papillary carcinoma presented the highest NADK expression score and the highest NADK intensity. The highest Fuhrman grade was also associated with the percentage of labeled cells and the NADK expression score. Furthermore, a significant positive correlation was observed between G6PD and NADK expression scores. The results suggest that NADK and G6PD are enzymes associated with pRCC and higher Fuhrman grades. G6PD appears to have greater potential as a marker of tumor aggressiveness, especially for size and presence of necrosis in the ccRCC.