肝细胞癌患者内质网应激凋亡信号通路的性别差异肝细胞癌患者内质网应激凋亡信号通路的性别差异

冯敏, 丁杰, 刘颂, 田晶, 孙本龙, 管文贤

江苏大学学报(医学版) ›› 2017, Vol. 27 ›› Issue (5) : 432-436.

PDF(1482 KB)
中国科技核心期刊
中国应用型核心期刊
中国医药卫生核心期刊
中国高校优秀科技期刊
美国《化学文摘(CA)》收录
美国《剑桥科学文摘(CSA)》收录
波兰《哥白尼索引(IC)》收录
日本科学技术振兴机构数据库(JST)收录
PDF(1482 KB)
江苏大学学报(医学版) ›› 2017, Vol. 27 ›› Issue (5) : 432-436.
临床医学

肝细胞癌患者内质网应激凋亡信号通路的性别差异肝细胞癌患者内质网应激凋亡信号通路的性别差异

  • 冯敏, 丁杰, 刘颂, 田晶, 孙本龙, 管文贤
作者信息 +

Gender difference in endoplasmic reticulum stress and apoptosis signals in patients with hepatocellular carcinoma

  • FENG Min, DING Jie, LIU Song, TIAN Jing, SUN Ben-long, GUAN Wen-xian
Author information +

摘要

目的:  评估内质网应激凋亡信号通路与肝细胞癌患者性别的相关性。方法: 回顾分析肝细胞癌术后病例,随机抽取男性及女性患者各40例手术切除的肝癌组织标本,同时纳入10例肝血管瘤手术切除的标本作为对照。蛋白质印迹法检测手术标本内质网应激凋亡信号通路各蛋白的表达量。分析年龄、性别、TNM分期、Child分级、肿瘤分化程度以及是否合并乙型肝炎、肝硬化与内质网应激凋亡通路蛋白表达的相关性。结果:  肝细胞癌组织内包括葡萄糖调节蛋白78(GRP78),GRP94, 剪切型X盒结合蛋白1(spliced Xbox binding protein 1,sXBP1),I型内质网跨膜激酶(typeI ER transmembrane protein kinase, IRE1α),转录激活因子6(activating transcription factor6(ATF6),C/EBP同源蛋白(C/EBP homologous protein,CHOP)和Caspas3的内质网应激及凋亡信号均明显强于对照组(均P<0.05)。年龄、分期、是否合并肝炎、肝硬化以及Child分级因素对肝细胞癌组织内质网应激信号无明显影响。与女性患者相比,男性病例包括sXBP1, ATF6, CHOP和Caspase3的内质网应激凋亡信号显著增强(均P<0.05);与中、高分化组比较,低分化组ATF6的表达明显下降(均P<0.05)。但进一步分层分析结果显示,分化程度对内质网应激信号ATF6无明显影响。结论: 男性病例肝细胞癌组织内质网应激凋亡信号比女性病例明显增强。

Abstract

Objective: To investigate the effect of gender on endoplasmic reticulumstress(ERstress) and apoptosis signals in patients with hepatocellular carcinoma. Methods: Clinical data was collected and retrospectively analyzed from 80 routine hepatocellular carcinoma(HCC) patients, including 40 male and 40 female. Normal liver parenchymal tissues were obtained as controls from 10 Chinese patients with hemangioma.The clinical typing of tumors was determined according to the TNM classification system. The histological grade of tumor differentiation was evaluated by the Edmondson grading system and liver function was assessed by ChildPugh score system. Characteristics of ERstress and apoptosis signal in patients and controls were analyzed by Western blotting. Results: The levels of ERstress signal factors including glucose regulated protein 78(GRP78),GRP94,spliced X boxbinding protein 1(sXBP1), activating transcription factor 6(ATF6),inositol requiring enzyme 1(IRE1α),C/EBP homologous protein(CHOP) were elevated significantly compared with control(P<0.05). Meanwhile, the level of Caspase3 was increased in HCC patients.The clinic features,such as stage, HBV infection, liver cirrhosis and Child grade had on obvious effect on ERstress signal.Only had age affected on GRP78 levels rather than other ERstress signal factors. Interestingly,the levels of sXBP1, ATF6, CHOP and Caspase3 elevated significantly, while GRP78 level reduced in male patients compared with those of the female(P<0.05). ATF6 was also reduced significantly in poorlydifferentiated patients(P<0.05).Further studies indicated that differentiation had no effect on ERstress and apoptosis signals. Conclusion: ERstress and apoptosis signals were induced and GRP78 level was increased in male HCC patients. These results provided a preliminary data for personalized therapy based on gender.

关键词

肝细胞癌 / 内质网应激 / 凋亡

引用本文

导出引用
冯敏, 丁杰, 刘颂, 田晶, 孙本龙, 管文贤. 肝细胞癌患者内质网应激凋亡信号通路的性别差异肝细胞癌患者内质网应激凋亡信号通路的性别差异[J]. 江苏大学学报(医学版), 2017, 27(5): 432-436
FENG Min, DING Jie, LIU Song, TIAN Jing, SUN Ben-long, GUAN Wen-xian. Gender difference in endoplasmic reticulum stress and apoptosis signals in patients with hepatocellular carcinoma[J]. Journal of Jiangsu University(Medicine Edition), 2017, 27(5): 432-436

参考文献

[1]Duffy AG,Greten TF.Liver cancer: Regorafenib as secondline therapy in hepatocellular carcinomaJ.Nat Rev Gastroenterol Hepatol,2017,14(3):141-142.
[2]Li CL,Yeh KH,Liu WH, et al.Elevated p53 promotes the processing of miR18a to decrease estrogen receptoralpha in female hepatocellular carcinomaJ.Int J Cancer,2015, 136(4):761-770.
[3]Li T,Qin LX,Gong X,et al.Clinical characteristics, outcome, and risk factors for early and late intrahepatic recurrence of female patients after curative resection of hepatocellular carcinomaJ.Surgery,2014,156(3):651-660.
[4]Zou X, Qu Z,Fang Y,et al. Endoplasmic reticulum stress mediates sulforaphaneinduced apoptosis of HepG2 human hepatocellular carcinoma cellsJ.Mol Med Rep,2017,15(1): 331-338.
[5]Zhong J,Xiu P,Dong X,et al.Meloxicam combined with sorafenib synergistically inhibits tumor growth of human hepatocellular carcinoma cells via ER stressrelated apoptosisJ. Oncol Rep,2015,34(4):2142-2150.
[6]Yang N,Fu Y,Zhang H,et al.LincRNAp21 activates endoplasmic reticulum stress and inhibits hepatocellular carcinomaJ.Oncotarget,2015,6(29):28151-28163.
[7]Han H,Hu J,Lau MY,et al.Altered methylation and expression of ERassociated degradation factors in longterm alcohol and constitutive ER stressinduced murine hepatic tumorsJ. Front Genet,2013,4:224.
[8]Wang Q,Yu T,Yuan Y,et al.Sorafenib reduces hepatic infiltrated regulatory T cells in hepatocellular carcinoma patients by suppressing TGFβ signalJ.J Surg Oncol, 2013,107(4):422-427.
[9]Kao E, Shinohara M,Feng M,et al.Human immunodeficiency virus protease inhibitors modulate Ca2+ homeostasis and potentiate alcoholic stress and injury in mice and primary mouse and human hepatocytesJ.Hepatology,2012,56(2):594-604.
[10]Gao J,Jiang Z,Wang S,et al. Endoplasmic reticulum stress of Kupffer cells involved in the conversion of natural regulatory T cells to Th17 cells in liver ischemiareperfusion injuryJ.J Gastroenterol Hepatol,2016,31(4):883-889.
[11]Yang Y,Wang G,He J,et al.Gender differences in colorectal cancer survival: A metaanalysisJ.Int J Cancer,2017.doi:10.1002/ijc.30827.Epubaheadofprint
[12]Isla D,Majem M,Vinolas N,et al.A consensus statement on the gender perspective in lung cancerJ.Clin Transl Oncol,2017,19(5):527-535.
[13]Lucca I,Klatte T,Fajkovic H,et al.Gender differences in incidence and outcomes of urothelial and kidney cancerJ.Nat Rev Urol,2015,12(10):585-592.
[14]Jung EM, An BS, Choi KC,et al.Apoptosis and endoplasmic reticulum stressrelated genes were regulated by estrogen and progesterone in the uteri of calbindinD(9k) and D(28k) knockout miceJ.J Cell Biochem,2012,113(1):194-203.
[15]Shuda M, Kondoh N, Imazeki N,et al.Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesisJ.J Hepatol,2003,38(5):605-614.

基金

国家自然科学基金资助项目(81670561);江苏省六大人才项目(2014WSW046);南京市医学发展杰出青年基金资助项目(JQX14003)


PDF(1482 KB)

73

Accesses

0

Citation

Detail

段落导航
相关文章

/