Progesterone receptor membrane component 1 as a potential prognostic biomarker for hepatocellular carcinoma

Abstract

AIMTo investigate the clinicopathological significance of progesterone receptor membrane component 1 (PGRMC1) and PGRMC2 in hepatocellular carcinoma (HCC).METHODSWe performed immunohistochemical staining to evaluate the estrogen receptor (ER), progesterone receptor (PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data (n = 373) from The Cancer Genome Atlas (TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients. We knocked down or overexpressed PGRMC1 in HCC cell lines to evaluate its biological significance in HCC cell proliferation, differentiation, migration, and invasion.RESULTSWe found that few HCC cases expressed ER (5.6%) and PR (4.5%). In contrast, most HCC cases expressed PGRMC1 (89.9%) and PGRMC2 (100%). PGRMC1 and PGRMC2 exhibited significantly lower expression in tumor tissue than in non-tumor tissue (P < 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression (P = 0.004), poorer tumor differentiation (P = 0.045) and liver capsule penetration (P = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival (P = 0.002, HR = 2.384, CI: 1.377-4.128) in our cases, as well as in the TCGA cohort (P < 0.001, HR = 2.857, CI: 1.781-4.584). The expression of PGRMC2 did not relate to patient outcome. PGRMC1 knockdown promoted a poorly differentiated phenotype and proliferation of HCC cells in vitro, while PGRMC1 overexpression caused the opposite effects.CONCLUSIONPGRMC1 is a non-classical hormonal receptor that negatively regulates hepatocarcinogenesis. PGRMC1 down-regulation is associated with progression of HCC and is a poor prognostic indicator.

Progesterone suppresses the progression of colonic carcinoma by increasing the activity of the GADD45α/JNK/c‑Jun signalling pathway

“…1A ). Progesterone plays an essential role in physiological and pathological processes through activation of the PGR ( 5 ). Thus, IHC staining was performed in colorectal tumour tissues ( Fig.…”

“…Progesterone, an important natural sex hormone, is involved in the menstrual cycle, pregnancy and embryogenesis of humans ( 4 ). Its cellular effects are mediated by binding to the progesterone receptor (PGR) and regulating hormone response target genes in several cancer types, such as liver ( 5 ), ovarian ( 6 ), gastric ( 7 ) and breast ( 8 ) cancer. Furthermore, progesterone regulates various cancer cell phenotypes, including proliferation, apoptosis, angiogenesis and autophagy ( 9 ).…”

Hormone Replacement Therapy in Cancer Survivors – Review of the Literature

“…Estrogen receptor overexpression, however, has not only been found in the well-known estrogen dependent tumour types, such as breast, endometrial and ovarian cancer. Altered estrogen and / or progesterone receptor expression has been documented for example in thyroid cancer [12][13][14][15], Hodgkin's lymphoma [16][17][18], B-cell malignancies [19,20], brain tumours [21][22][23][24][25], prolactinoma [26,27], melanoma [28][29][30][31], lung cancer [32,33], colorectal cancer [34][35][36], gastric cancer [37] and liver cancer [38,39].…”

HNF-1 binding point mutation of the AFP gene promotes cirrhosis in post-menopausal women

“…The AFP promoter is located in the 200 bp region upstream of the gene, 11 where there are many binding sites of transcriptional regulatory factors, which are related to the regulation of AFP. 12,13 The AFP promoter region has two hepatocyte nuclear factor-1 (HNF-1) binding sites and non-tissue-specific NF-1 binding sites partially overlap with C/EBP and HNF1 binding sites. Low concentration of NF-1 produces a weak activation effect on the AFP promoter, while high concentration inhibits promoter activity.…”