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

Hung Wen Tsai, Chung Liang Ho, Shu Wen Cheng, Yih Jyh Lin, Chou Cheng Chen, Pin Nan Cheng, Chia Jui Yen, Ting Tsung Chang, Po Min Chiang, Shih Huang Chan, Cheng Hsun Ho, Shu Hui Chen, Yi Wen Wang, Nan Haw Chow, Jou Chun Lin

研究成果: Article同行評審

24 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)1152-1166
期刊World journal of gastroenterology
出版狀態Published - 2018 3月 14

All Science Journal Classification (ASJC) codes

  • 消化內科


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