Cancers, Vol. 11, Pages 1602: Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma

In this study, we investigated the prognostic significance of pAMPK with respect to subcellular location and investigated its interaction with TGF-β/SMAD in ccRCC. Immunohistochemical staining for pAMPK, pSMAD2 and SMAD4 was conducted on tissue microarray of 987 ccRCC specimens. Moreover, the levels of pSMAD2 were measured in Caki-1 cells treated with 5-aminoimidazole-4-carboxamide ribonucleotide. The relationship between AMPK/pAMPK and TGFB1 expression was determined using the TCGA database. As a result, pAMPK positivity, either in the cytoplasm or nuclei, was independently associated with improved ccRCC prognosis, after adjusting for TNM stage and WHO grade. Furthermore, pAMPK-positive ccRCC displayed increased pSMAD2 and SMAD4 expression, while activation of pAMPK increased pSMAD2 in Caki-1 cells. However, AMPK/pAMPK expression was inversely correlated with TGFB1 expression in the TCGA database. Therefore, pAMPK immunostaining, both in the cytoplasm and nuclei, is a useful prognostic biomarker for ccRCC. pAMPK targets TGF-β-independent phosphorylation of SMAD2 and activates pSMAD2/SMAD4, representing a novel anti-tumoral mechanism of pAMPK in ccRCC.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research