骨桥蛋白在不同病理分期原发性胆汁性胆管炎的表达特点分析

肝脏 ›› 2022, Vol. 27 ›› Issue (6): 693-697.

骨桥蛋白在不同病理分期原发性胆汁性胆管炎的表达特点分析

王彦坤, 马俊骥

100069 首都医科大学附属北京佑安医院病理科(王彦坤);河北医科大学第二医院消化内科河北省消化病实验室河北省消化病研究所(马俊骥)

收稿日期:2021-09-29 出版日期:2022-06-30 发布日期:2022-08-04
通讯作者: 马俊骥,Email: majunji2006@163.com
基金资助:
河北省自然科学基金资助项目(H2015206431)

Expression of osteopontin in different pathological stages of primary biliary cholangitis

WANG Yan-kun¹, MA Jun-ji²

1. Department of Pathology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China;
2. Department of Gastroenterology, the Second Hospital of Hebei Medical University, the Hebei Key Laboratory of Gastroenterology, the Hebei Institute of Gastroenterology, Shijiazhuang 050000, China

Received:2021-09-29 Online:2022-06-30 Published:2022-08-04
Contact: MA Jun-ji,Email: majunji2006@163.com

摘要/Abstract

摘要： 目的探讨骨桥蛋白(OPN)在原发性胆汁性胆管炎(PBC)进展过程中的作用。方法回顾性分析2013年12月至2020年1月首都医科大学附属北京佑安医院70例PBC患者的临床资料。HE、Masson和Gomori银染方法评估PBC肝脏不同病理分期组织病变和纤维化。CK19、CK7和OPN抗体用来研究PBC肝组织胆管损伤情况和OPN表达特点。采用非参数Spearman相关分析PBC病理分期与OPN病理评分之间的相关性。结果 70例PBC患者血清抗线粒体抗体(anti-mitochondrial antibody, AMA )均阳性。女性和男性比例为6∶1。PBC病理分期1-4期分别为18例,17例,18例和17例,年龄分别为(48±12)岁,(48±12)岁,(53±9)岁和(56±7)岁。与1期PBC患者年龄相比,4期年龄较大,差异有统计学意义(P=0.026)。随着PBC病程进展,肝纤维化和胆管损伤逐渐加重。与PBC病理1期(χ²=12.586, P<0.01)、2期(χ²=21.394, P<0.001)和4期(χ²=4.972, P=0.026)相比,OPN免疫组化评分强表达的比例在3期PBC明显升高,达到83.33%。OPN阳性细胞在1期PBC汇管区偶尔可以看到,而与1期PBC的不同,在2期至4期PBC肝组织汇管区中OPN阳性细胞数均明显增多。采用非参数Spearman相关分析发现,PBC病理分期与OPN病理评分具有一定的相关性(r=0.396, P=0.001)。结论 PBC发展到肝纤维化后,OPN在肝组织中的表达量明显增加,肝硬化期后OPN高表达比率降低。OPN高表达提示胆管免疫损伤负荷加重,同时也预示肝组织增生能力较强。OPN与PBC病理分期密切结合对于评估病情严重程度及患者预后有重要的价值。

关键词: 原发性胆汁性胆管炎, 肝脏病理分期, 骨桥蛋白

Abstract: Objective To detect the expression of osteopontin (OPN) in liver tissues at different pathological stages of primary biliary cholangitis (PBC), and to explore the role of OPN in the PBC progression.Methods A retrospective analysis of the liver pathology of the Department of Pathology, Beijing You’an Hospital, Capital Medical University, from December 2013 to January 2020. HE, Masson and Gomori silver staining were combined to evaluate the pathological changes and fibrosis of PBC liver at different pathological stages. CK19, CK7 and OPN antibodies were used to study bile duct injury and OPN expression in PBC liver tissue. Nonparametric Spearman correlation was used to analyze the correlation between PBC pathological stage and OPN pathological score.Results A total of 70 PBC cases were included. The serum anti-mitochondrial antibody (AMA) was positive, including 10 males (14.29%), with an average age of (53 ± 9) years and 60 females (85.71%) , the average age was (51 ± 11) years old, and the ratio of female to male was 6:1. The patients with PBC pathological stages 1-4 were 18, 17, 18 and 17 respectively, and the average ages were (48 ± 12) years old, (48 ± 12) years old, (53 ± 9) years old and (56 ± 7) years old respectively. Compared with the average age of patients with PBC stage 1, the patients with stage 4 were older (P=0.026). With the progression of PBC, hepatic fibrosis and bile duct injury gradually aggravated. Compared with PBC pathological stage 1 (χ²=12.586, P<0.001) and stage 2 (χ²=21.394, P<0.001) and stage 4 (χ²=4.972, P=0.026), the rate of strong expression of OPN immunohistochemical score increased significantly in PBC pathological stage 3 (83.33%). OPN positive cells could be seen occasionally in stage 1 PBC portal area, but different from stage 1 PBC, the number of OPN positive cells in stage 2 to 4 PBC liver portal area increased significantly. Nonparametric Spearman correlation analysis showed that there was a certain correlation between PBC pathological stage and OPN pathological score (r=0.396, P=0.001).Conclusion After PBC developes into hepatic fibrosis, the expression of OPN in liver tissue increases significantly, and the high expression rate of OPN decreases after liver cirrhosis. The high expression of OPN not only indicates the aggravation of bile duct immune injury load, but also indicates the strong ability of liver tissue proliferation. The close combination of OPN and PBC pathological stage has important clinical value for evaluating the severity of the disease and predicting the prognosis of patients.

Key words: Primary biliary cholangitis, Liver pathological stage, Osteopontin

王彦坤, 马俊骥. 骨桥蛋白在不同病理分期原发性胆汁性胆管炎的表达特点分析[J]. 肝脏, 2022, 27(6): 693-697.

WANG Yan-kun, MA Jun-ji. Expression of osteopontin in different pathological stages of primary biliary cholangitis[J]. Chinese Hepatolgy, 2022, 27(6): 693-697.

参考文献

[1] Gulamhusein AF, Hirschfield GM. Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol, 2020, 17(2): 93-110.
[2] Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology, 2019, 69(1): 394-419.
[3] Song Z, Chen W, Athavale D, et al. Osteopontin takes center stage in chronic liver disease. Hepatology, 2021, 73(4):1594-1608.
[4] 杨依娜, 朱娅梅, 马世武. 骨桥蛋白在慢性肝病发病机制中的作用. 肝脏, 2021, 26(6): 594-596.
[5] Gimba ERP, Brum MCM, Nestal De Moraes G. Full-length osteopontin and its splice variants as modulators of chemoresistance and radioresistance (Review). Int J Oncol, 2019, 54: 420-430.
[6] Tibaldi E, Brocca A, Sticca A, et al. Fam20C-mediated phosphorylation of osteopontin is critical for its secretion but dispensable for its action as a cytokine in the activation of hepatic stellate cells in liver fibrogenesis. FASEB J, 2020, 34(1):1122-1135.
[7] Khajehahmadi Z, Mohagheghi S, Nikeghbalian S, et al. Liver stiffness correlates with serum osteopontin and TAZ expression in human liver cirrhosis. Ann N Y Acad Sci, 2020, 1465(1): 117-131.
[8] Kwon H, Song K, Han C, et al. Inhibition of hedgehog signaling ameliorates hepatic inflammation in mice with nonalcoholic fatty liver disease. Hepatology, 2016, 63(4): 1155-1169.
[9] Nardo AD, Grün NG, Zeyda M, et al. Impact of osteopontin on the development of non-alcoholic liver disease and related hepatocellular carcinoma. Liver Int, 2020, 40(7): 1620-1633.
[10] Harada K, Ozaki S, Sudo Y, et al. Osteopontin is involved in the formation of epithelioid granuloma and bile duct injury in primary biliary cirrhosis. Pathol Int, 2003, 53: 8-17.
[11] Cielecka-Kuszyk J, Janowska M, Markiewicz M, et al. The usefulness of immunohistochemical staining of bile tracts in biliary atresia. Clin Exp Hepatol, 2021, 7(1): 41-46.
[12] 王彦坤, 马俊骥, 张明. 细胞角蛋白7在肝硬化病理诊断中的作用. 临床荟萃, 2019, 34(2): 124-127.
[13] Carbone M, Nardi A, Flack S, et al. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score. Lancet Gastroenterol Hepatol, 2018, 3(9): 626-634.
[14] Coppola D, Szabo M, Boulware D, et al. Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res, 2004, 10(1Pt1): 184-190.
[15] Lu M, Zhou Y, Haller IV, et al. Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment. Clin Gastroenterol Hepatol, 2018, 16(8): 1342-1350.e1.
[16] Gazda J, Drazilova S, Janicko M, et al. The epidemiology of primary biliary cholangitis in european countries: a systematic review and meta-analysis. Can J Gastroenterol Hepatol, 2021, 2021: 9151525.