The androgen receptor expression and its activity have different relationships with prognosis in hepatocellular carcinoma

Abstract

The role of the Androgen Receptor (AR) expression and its activity in the prognosis of hepatocellular carcinoma (HCC) remains inconclusive. The aim of this study is to analyze the role of the AR expression and its activity as prognostic biomarkers in HCC. Three-hundred and thirty-seven patients from The Cancer Genome Atlas (TCGA) (107 females; 59.42 years [SD = 13.0]) were included. To infer AR activity, the expression-profile of previously validated androgen responsive genes (ARGs) was included. AR activity was shown by the AR-Score-21 (21 ARGs) and AR-Score-13 (13 ARGs) that were computed based on the expression of the selected ARGs. Those ARGs whose expression was significantly different between histological grades were used for computing two new AR-Scores. HCC patients with higher AR expression showed a higher median overall survival (OS). AR-Score 21 and AR-Score-13 did not show any association with prognosis. Six of the 21 ARGs of the AR-Score-21 and 7 of the 13 ARGs of the AR-Score-13 showed a significant different expression profile among histological grades. Based on these differences, another two AR-Scores were computed (AR-Score-6 and AR-Score-7). They showed the relative increase of upregulated to downregulated ARGs in high-grade HCC. Higher AR activity inferred by these AR-Scores was associated with worse outcomes. The expression of AR is associated with a better prognosis in HCC. However, the activity of the AR seems to be qualitatively different among histological grades. The AR activity inferred by the shifted ARGs is associated with a worse prognosis in HCC patients.

No impact of donor sex on the recurrence of hepatocellular carcinoma after liver transplantation

“…In the nontransplant setting, studies have suggested that sex hormone receptors in the liver mediate most sex disparities in HCC 5,[23][24][25][26] although some other studies have suggested that sex hormones themselves can mediate it 6,27 In the former case, it is reasonably assumed that the difference in overall recurrence rate after LT, if it exists, is attributable to the difference in graft recurrence rate. We specifically analyzed the graft recurrence rate to assess this possibility with higher sensitivity.…”

Molecular Features of Androgen-Receptor Low, Estrogen Receptor-Negative Breast Cancers in the Carolina Breast Cancer Study

“…We also did not evaluate protein-level AR localization compared to our multigene classi er. However previous studies show that AR RNA-based signatures expression correlate with AR protein expression [55,56].…”

Investigation of Anti-Liver Cancer Activity of the Herbal Drug FDY003 Using Network Pharmacology

“…AKT1 is an important regulator of the tumorigenic processes, migration, Evidence-Based Complementary and Alternative Medicine spreading, therapeutic sensitivity, resistance, survival, and proliferation of LC cells, and is a promising theragnostic target [64][65][66][67]. AR expression and activity influence angiogenesis, stemness, invasion, angiogenesis, epithelialmesenchymal transition (EMT), migration, and oncogenesis of LC cells, and it is a prognostic determinant and responsive marker for anticancer therapies [68][69][70][71][72][73]. EGFR is responsible for the modulation of proliferation, metastasis, migration, self-renewal potential, EMT, angiogenesis, anchorage-independent growth, invasion, and drug sensitivity of LC cells and tumors, and its expression and activity are implicated in the initiation, recurrence, progression, metastasis, and aggressiveness of LC in patients [74][75][76][77][78][79][80][81][82][83].…”