肝癌為全球最致命的惡性腫瘤且治療方式有限的癌症之一，其主要的危險因子有 B 型肝炎、C 型肝炎、酒精性肝病和非酒精性脂肪肝病。近年出現許多以訊息傳遞分子為標的之標靶治療抑制劑，例如：以 EGFR 為標靶的 Gefitinib 及 Erlotinib 和以 MET 為標靶的 SU11274。就這一點而言，膜受體對於分子標靶治療來說是一好的標靶，且對於在未來分析每個肝癌病人其分子的表現譜，進而選擇合適的標靶治療也是越來越重要的。罹患肝癌的機率為男性高於女性，而此現象進一步被臨床的觀察所支持，即患有慢性肝病的男性會比女性較快速的發展成肝硬化，因此肝硬化導致肝癌的發生被認為主要是男性及停經的女性的疾病。然而，男性和女性的性荷爾蒙及其受體在肝癌中的確切作用仍知之甚少。
為了尋找與肝癌相關之新的生物標誌，我們利用肝癌和鄰近非腫瘤的肝組織進行 MALDI-IMS 及 SDS-PAGE 之實驗。且透過 in-gel digestion 與 MS/MS 之分析找出幾個有興趣的基因，其中包含屬於 MAPR family 的孕酮受體膜蛋白單元 1 (progesterone receptor membrane component 1, PGRMC1)。PGRMC1 為膜上黃體素受體 (membrane progesterone receptor) 其中的一員且最初由豬的肝臟分離出來。PGRMC1 是一較小蛋白質 (25 kDa)，其整個 PGRMC1 分子為黃體素的結合與反應所需的。PGRMC1 被視為腫瘤細胞增生的生物標誌，且大量的表現於不同的癌症中，例如：卵巢癌、乳癌及肺癌。臨床上，我們發現 PGRMC1 的表現量若在肝癌組織中為下降的話，其與較差的無病生存期有關。在體外實驗中，我們將肝癌細胞株利用 knockdown 及 overexpression 的方式並進一步探討 PGRMC1 與 EMT、癌幹性、細胞增生、抗藥性 (將5-fluorouracil 加入細胞中) 及自噬作用之間的相關。藉由西方墨點法發現 PGRMC1 與 EMT 及癌幹性都無相關，然而，其與自噬作用似乎有相關性。最後，利用 XTT 分析後發現 PGRMC1 與肝癌細胞的增生及抗藥性有關，若過度表現 PGRMC1，則肝癌細胞的增生及抗藥性會下降；反之，若 knockdown PGRMC1，肝癌細胞的增生及抗藥性則會上升。

To identify novel biomarkers associated with HCC, we have performed both MALDI-imaging and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) on histology-proven HCC and adjacent non-tumor liver tissues. In-gel digestion with tandem mass spectrometry identified several interesting genes, including progesterone receptor membrane component 1 (PGRMC1) that belongs to membrane-associated progesterone receptor (MAPR) family. By using clinical specimen, we found that PGRMC1 is down-regulated in many HCC tissues which correlates with worse disease-free survival. In vitro, we used knockdown and overexpression approaches in the HCC cell lines to further evaluate the role of PGRMC1 in epithelial-mesenchymal transition (EMT), cancer stemness, cell proliferation, drug resistance, and autophagy. We found that PGRMC1 was neither associated with epithelial-mesenchymal transition (EMT) nor cancer stemness by western blot analysis. However, it seemed related with autophagy. Furthermore, PGRMC1 was related with cell proliferation and drug resistance through XTT assay. PGRMC1 overexpression decreased cell proliferation and reduced drug resistance in HCC cell lines. On the other hand, PGRMC1 knockdown increased cell proliferation and enhanced drug resistance in HCC cell lines.

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