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Progesterone receptor membrane component 1 as a potential prognostic biomarker for hepatocellular carcinoma
- Source :
- World Journal of Gastroenterology
- Publication Year :
- 2018
- Publisher :
- Baishideng Publishing Group Inc., 2018.
-
Abstract
- AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1 (PGRMC1) and PGRMC2 in hepatocellular carcinoma (HCC). METHODS We 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. RESULTS We 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. CONCLUSION PGRMC1 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.
- Subjects :
- Male
0301 basic medicine
Carcinoma, Hepatocellular
Carcinogenesis
Hepatocellular carcinoma
Proliferation
Down-Regulation
Clinical Practice Study
Disease-Free Survival
03 medical and health sciences
0302 clinical medicine
Cell Movement
Progesterone receptor
Biomarkers, Tumor
medicine
Humans
Prognostic biomarker
Cell Proliferation
business.industry
Liver Neoplasms
Gastroenterology
Membrane Proteins
Cell Differentiation
Hep G2 Cells
General Medicine
Middle Aged
Progesterone receptor membrane component 1
Prognosis
medicine.disease
digestive system diseases
Gene Expression Regulation, Neoplastic
030104 developmental biology
Membrane
Liver
Receptors, Estrogen
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Cancer research
Female
Hormonal receptor
Receptors, Progesterone
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 10079327
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- World Journal of Gastroenterology
- Accession number :
- edsair.doi.dedup.....1ee5fee7bdc3feb44b440e4c3e082ccc