Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
World J Gastroenterol. 2018 Mar 14;24(10):1152-1166. doi: 10.3748/wjg.v24.i10.1152.
To investigate the clinicopathological significance of progesterone receptor membrane component 1 (PGRMC1) and PGRMC2 in hepatocellular carcinoma (HCC).
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 ( = 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.
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 ( < 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression ( = 0.004), poorer tumor differentiation ( = 0.045) and liver capsule penetration ( = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival ( = 0.002, HR = 2.384, CI: 1.377-4.128) in our cases, as well as in the TCGA cohort ( < 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 , while PGRMC1 overexpression caused the opposite effects.
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.
研究孕激素受体膜组份 1（PGRMC1）和 PGRMC2 在肝细胞癌（HCC）中的临床病理意义。
我们对 89 对 HCC 和非肿瘤肝样本的临床队列进行了免疫组织化学染色，以评估雌激素受体（ER）、孕激素受体（PR）、PGRMC1 和 PGRMC2 的表达。我们还分析了来自癌症基因组图谱（TCGA）的 HCC 数据（n=373）。我们将 PGRMC1 和 PGRMC2 的表达状态与 HCC 患者的临床病理指标和临床结局相关联。我们在 HCC 细胞系中敲低或过表达 PGRMC1，以评估其在 HCC 细胞增殖、分化、迁移和侵袭中的生物学意义。
我们发现，少数 HCC 病例表达 ER（5.6%）和 PR（4.5%）。相比之下，大多数 HCC 病例表达 PGRMC1（89.9%）和 PGRMC2（100%）。PGRMC1 和 PGRMC2 在肿瘤组织中的表达明显低于非肿瘤组织（<0.001）。HCC 中 PGRMC1 表达较低与血清甲胎蛋白表达较高（=0.004）、肿瘤分化较差（=0.045）和肝包膜穿透（=0.038）显著相关。在我们的病例中以及 TCGA 队列中，低 PGRMC1 表达是无病生存较差的独立预测因子（=0.002，HR=2.384，CI：1.377-4.128）（<0.001，HR=2.857，CI：1.781-4.584）。PGRMC2 的表达与患者预后无关。PGRMC1 敲低促进 HCC 细胞向低分化表型和增殖，而 PGRMC1 过表达则产生相反的效果。
PGRMC1 是一种非经典的激素受体，负调节肝癌发生。PGRMC1 的下调与 HCC 的进展有关，是预后不良的指标。
