一种新型的胰腺癌预后标志物和免疫原性膜抗原：抑制素（PHB）。
A novel prognostic marker and immunogenic membrane antigen: prohibitin (PHB) in pancreatic cancer.
机构信息
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 1 Shuai Fu Yuan Hu Tong, Beijing, 100730, China.
Department of General Surgery, Beijing Tsinghua Chang Gung Hospital, Tsinghua University, 168 soup road, Changping District, Beijing, 102218, China.
出版信息
Clin Transl Gastroenterol. 2018 Sep 6;9(9):178. doi: 10.1038/s41424-018-0044-1.
BACKGROUND
Previous study, using immunoblotting with IgG and membrane proteins, identified prohibitin (PHB) as a potential immunogenic membrane antigen. Now, investigate PHB expression and biological functions in pancreatic cancer.
METHODS
PHB expression was analysed in PDAC cell lines, normal pancreas tissues, cancer tissues, PDAC patient sera and healthy volunteer sera using QRT-PCR, Western blotting, IHC, and ELISA, and a survival analysis and a COX regression analysis were performed. Low and high PHB expression levels were accomplished using RNA interference technology and gene transfer techniques. Cell proliferation, migration, and invasion, apoptosis-related proteins were assessed 48 h after transfection.
RESULTS
PHB was generally expressed in the 8 tested PDAC cell lines. PHB was significantly increased in PDAC tissues and negatively correlated with overall survival (p < 0.01). PHB was an independent prognostic factor in PDAC (p < 0.01). PHB was increased in PDAC patient sera (p < 0.01). siRNA-PHB decreased cell growth, migration and invasion. However, PHB overexpression resulted in the opposite effects. Western blotting and Flow cytometric analysis revealed apoptosis inhibition in siRNA-PHB PDAC cells.
CONCLUSIONS
PHB plays a key role in modulating the malignant phenotype and apoptosis induction, which may be a novel prognostic predictor and a candidate for targeted therapy against PDAC.
背景
先前的研究使用 IgG 和膜蛋白的免疫印迹法，鉴定出抑素（PHB）为一种潜在的免疫原性膜抗原。本研究旨在研究 PHB 在胰腺癌中的表达和生物学功能。
方法
使用 QRT-PCR、Western blot、免疫组化和 ELISA 分析 PDAC 细胞系、正常胰腺组织、癌症组织、PDAC 患者血清和健康志愿者血清中的 PHB 表达，并进行生存分析和 COX 回归分析。使用 RNA 干扰技术和基因转移技术实现低和高 PHB 表达水平。转染 48 小时后评估细胞增殖、迁移和侵袭、凋亡相关蛋白。
结果
PHB 在 8 种测试的 PDAC 细胞系中普遍表达。PHB 在 PDAC 组织中显著增加，与总生存期呈负相关（p<0.01）。PHB 是 PDAC 的独立预后因素（p<0.01）。PDAC 患者血清中 PHB 增加（p<0.01）。siRNA-PHB 降低了细胞生长、迁移和侵袭。然而，PHB 过表达则产生相反的效果。Western blot 和流式细胞术分析显示 siRNA-PHB PDAC 细胞中凋亡抑制。
结论
PHB 在调节恶性表型和诱导细胞凋亡中起着关键作用，可能是一种新的预后预测指标和针对 PDAC 的靶向治疗候选物。
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