Expressions and Significance of Hedgehog Ssignaling Pathway Protein of Ptch1 and Gli1 in Cholangiocarcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 WEIXi-lin ,  ZHOUZhong-xiao , ZHANGJian , BIANGang , LIJin-hui

Department of The Third General Surgery, Affiliated Hospital of Shenyang Medical Center General, Shenyang 110024, Liaoning Province, China;

Corresponding author：

ZHOUZhong-xiao, Email: 16738505@qq.com

Keywords：

Cholangiocarcinoma; Hedgehog signal transduction pathway; Ptch1 protein; Gli1 protein

DOI：

10.7507/1007-9424.20160018

Video：

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Objective To investigate the expressions of Patched-1 (Ptch1) and glioma-associated oncogene homologl (Gli1) protein of sonic hedgehog signaling pathway in cholangiocarcinoma tissues, and explore their correlations to the occurrence and development of cholangiocarcinoma. Methods The expressions of Ptch1 and Gli1 protein in 62 specimens of cholangiocarcinoma and its bile duct tissues adjacent to cancer were detected by immunohistochemistry, and their positive rate correlated with patients, age, tumor size, differentiation grade, tumor location, lymph node metastasis, TNM stage, operation mode, and postoperative survival time were investigated by statistical analysis. Results The positive rates of Ptch1 and Gli1 protein were significantly higher in cholangiocarcinoma than in tissues adjacent to cancer (74.2% vs. 14.5%, 88.7% vs. 9.7%, P < 0.05). The expressions of Ptch1 and Gli1 protein in cholangiocarcinoma had no correlation to patients age, tumor size, and tumor location (P > 0.05), but were correlated to the operation mode, differentiation grade, lymph node metastasis, TNM stage, and postoperative survival time of patients (P < 0.05). Conclusions The elevated expressions of Ptch1 and Gli1 protein of Hh signaling pathway participated in the occurrence and development of cholangiocarcinoma. They may be ideal targets for therapy against cholangiocarcinoma.

Citation： WEIXi-lin, ZHOUZhong-xiao, ZHANGJian, BIANGang, LIJin-hui. Expressions and Significance of Hedgehog Ssignaling Pathway Protein of Ptch1 and Gli1 in Cholangiocarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(1): 70-74. doi: 10.7507/1007-9424.20160018 Copy

1.	Morrione A, Neill T, Iozzo RV. Dichotomy of decorin activity on the insulin-like growth factor-Ⅰsystem. FEBS J, 2013, 280(10):2138-2149.
2.	薛立新, 李绪雄, 舒斌, 等.阻断Hedgehog信号通路可抑制胆管癌细胞QBC939的生长.中华肝胆外科杂志, 2013, 19(3):224-229.
3.	Omenetti A, Choi S, Michelotti G, et al. Hedgehog signaling in the liver. J Hepatol, 2011, 54(2):366-373.
4.	Lee CS, Buttitta L, Fan C M. Evidence that the WNT inducible growth arrest specific gene 1 encodes an antagonist of sonic hedgehog signaling in the somite. Proc Natl Acad Sci USA, 2001, 98(20):11347-11352.
5.	子树明, 高军, 杨明, 等.结肠癌中Hedgehog信号转导通路成员的表达及其意义.中国肿瘤生物治疗杂志, 2011, 18(5):539-543.
6.	王伟林, 余翔, 李泉, 等.过表达核心蛋白聚糖基因对胆管癌细胞周期及凋亡的影响.中华实验外科杂志, 2015, 32(1):69-71.
7.	魏洪亮, 丁志强, 俞亚红, 等.肝门部胆管癌中Shh和Ptch的表达与肿瘤侵袭性及根治术后复发的关系.华中科技大学学报:医学版, 2011, 40(2):213-217.
8.	祝珊珊, 李文岗.胆管癌相关信号通路的研究进展.世界华人消化杂志, 2012, 20(30):2913-2919.
9.	Fingas CD, Bronk SF, Werneburg NW, et al. Myofibroblast-derived PDGF-BB promotes Hedgehog survival signaling in cholangiocar-cinoma cells. Hepatology, 2011, 54(6):2076-2088.
10.	Jinawath A, Akiyama Y, Sripa B, et al. Dual blockade of the Hedgehog and ERK1/2 pathways coordinately decreases proliferation and survival of cholangiocarcinoma cells. J Cancer Res Clin Oncol, 2007, 133(4):271-278.
11.	虞玲华, 殷新光, 邬万新, 等.胆囊癌中Hedgehog信号通路效应蛋白的表达及临床意义.中华普通外科杂志, 2013, 28(12):968-969.
12.	郭杰芳, 高军, 李兆申, 等.胰腺癌中GLI1、PTCH1 mRNA的表达及其与临床指标相关性分析.中华胰腺病杂志, 2010, 10(3):196-198.
13.	余翔, 李泉, 毛永欢, 等.核心蛋白聚糖在胆管癌中的表达及其临床意义.中华实验外科杂志, 2014, 31(11):2384-2385.
14.	李晓亮, 肖燎原, 徐志飞, 等.胶质瘤相关癌基因蛋白在肿瘤发生中的作用.现代生物医学进展, 2014, 27(13):5384-5386.
15.	Tushar Patel. Cholangiocarcinoma-controversies and challenges. Nat Rev Gastroenterol Hepatol, 2011, 8(4):189-200.
16.	Zhang BY, Lu Y, Dong Q, et al. Surgical treatment and prognostic analysis of 93 cases of hilar cholangiocarcinoma. Am J Med Sci, 2010, 339(3):221-224.
17.	Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol, 2013, 14(7):416-429.
18.	董茂盛, 李振, 许小亚, 等.肝门部胆管癌神经浸润的病理学分析及临床意义探讨.中国普外基础与临床杂志, 2015, 22(2):212-215.
19.	刘民锋, 罗剑, 余险峰, 等. PTEN和mTOR信号转导通路在胆管癌发展中作用的研究.中国普通外科杂志, 2006, 15(4):274-276.
20.	胡骁, 胡维昱, 孙传东, 等.肝门部胆管癌根治性切除术后并发症的诊断和治疗.中国现代普通外科进展, 2015, 18(4):328-330.
21.	盛涛, 赵国刚, 徐建, 等. 150例肝外胆管癌的临床病理与预后分析.河北医学, 2015, 21(6):940-942.
22.	Rongyang Dai, Juanjuan Li, Jing Fu, et al. The tyrosine kinase c-Met contributes to the pro-tumorigenic function of the p38 kinase in human bile duct cholangiocarcinoma cells. J Biol Chem, 2012, 287(47):39812-39823.
23.	Boris Blechacz, Mina Komuta, Tania Roskams, et al. Clinical diag-nosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol, 2011, 8(9):512-522.
24.	Nataliya Razumilava, Sergio A. Gradilone, et al. Non-canonical Hedgehog signaling contributes to chemotaxis in cholangiocarcinoma. J Hepatol, 2014, 60(3):599-605.
25.	周良晶, 丁国平, 曹利平, 等.肝门部胆管癌不同分期方法的比较.中华普通外科杂志, 2015, 30(3):177-180.
26.	Kentaroh Yamamoto, Fumio Yamamoto, Atsuhiro Maeda, et al. Tubulopapillary adenoma of the gallbladder accompanied by bile duct tumor thrombus. World J Gastroenterol, 2014, 20(26):8736-8739.

1. Morrione A, Neill T, Iozzo RV. Dichotomy of decorin activity on the insulin-like growth factor-Ⅰsystem. FEBS J, 2013, 280(10):2138-2149.
2. 薛立新, 李绪雄, 舒斌, 等.阻断Hedgehog信号通路可抑制胆管癌细胞QBC939的生长.中华肝胆外科杂志, 2013, 19(3):224-229.
3. Omenetti A, Choi S, Michelotti G, et al. Hedgehog signaling in the liver. J Hepatol, 2011, 54(2):366-373.
4. Lee CS, Buttitta L, Fan C M. Evidence that the WNT inducible growth arrest specific gene 1 encodes an antagonist of sonic hedgehog signaling in the somite. Proc Natl Acad Sci USA, 2001, 98(20):11347-11352.
5. 子树明, 高军, 杨明, 等.结肠癌中Hedgehog信号转导通路成员的表达及其意义.中国肿瘤生物治疗杂志, 2011, 18(5):539-543.
6. 王伟林, 余翔, 李泉, 等.过表达核心蛋白聚糖基因对胆管癌细胞周期及凋亡的影响.中华实验外科杂志, 2015, 32(1):69-71.
7. 魏洪亮, 丁志强, 俞亚红, 等.肝门部胆管癌中Shh和Ptch的表达与肿瘤侵袭性及根治术后复发的关系.华中科技大学学报:医学版, 2011, 40(2):213-217.
8. 祝珊珊, 李文岗.胆管癌相关信号通路的研究进展.世界华人消化杂志, 2012, 20(30):2913-2919.
9. Fingas CD, Bronk SF, Werneburg NW, et al. Myofibroblast-derived PDGF-BB promotes Hedgehog survival signaling in cholangiocar-cinoma cells. Hepatology, 2011, 54(6):2076-2088.
10. Jinawath A, Akiyama Y, Sripa B, et al. Dual blockade of the Hedgehog and ERK1/2 pathways coordinately decreases proliferation and survival of cholangiocarcinoma cells. J Cancer Res Clin Oncol, 2007, 133(4):271-278.
11. 虞玲华, 殷新光, 邬万新, 等.胆囊癌中Hedgehog信号通路效应蛋白的表达及临床意义.中华普通外科杂志, 2013, 28(12):968-969.
12. 郭杰芳, 高军, 李兆申, 等.胰腺癌中GLI1、PTCH1 mRNA的表达及其与临床指标相关性分析.中华胰腺病杂志, 2010, 10(3):196-198.
13. 余翔, 李泉, 毛永欢, 等.核心蛋白聚糖在胆管癌中的表达及其临床意义.中华实验外科杂志, 2014, 31(11):2384-2385.
14. 李晓亮, 肖燎原, 徐志飞, 等.胶质瘤相关癌基因蛋白在肿瘤发生中的作用.现代生物医学进展, 2014, 27(13):5384-5386.
15. Tushar Patel. Cholangiocarcinoma-controversies and challenges. Nat Rev Gastroenterol Hepatol, 2011, 8(4):189-200.
16. Zhang BY, Lu Y, Dong Q, et al. Surgical treatment and prognostic analysis of 93 cases of hilar cholangiocarcinoma. Am J Med Sci, 2010, 339(3):221-224.
17. Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol, 2013, 14(7):416-429.
18. 董茂盛, 李振, 许小亚, 等.肝门部胆管癌神经浸润的病理学分析及临床意义探讨.中国普外基础与临床杂志, 2015, 22(2):212-215.
19. 刘民锋, 罗剑, 余险峰, 等. PTEN和mTOR信号转导通路在胆管癌发展中作用的研究.中国普通外科杂志, 2006, 15(4):274-276.
20. 胡骁, 胡维昱, 孙传东, 等.肝门部胆管癌根治性切除术后并发症的诊断和治疗.中国现代普通外科进展, 2015, 18(4):328-330.
21. 盛涛, 赵国刚, 徐建, 等. 150例肝外胆管癌的临床病理与预后分析.河北医学, 2015, 21(6):940-942.
22. Rongyang Dai, Juanjuan Li, Jing Fu, et al. The tyrosine kinase c-Met contributes to the pro-tumorigenic function of the p38 kinase in human bile duct cholangiocarcinoma cells. J Biol Chem, 2012, 287(47):39812-39823.
23. Boris Blechacz, Mina Komuta, Tania Roskams, et al. Clinical diag-nosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol, 2011, 8(9):512-522.
24. Nataliya Razumilava, Sergio A. Gradilone, et al. Non-canonical Hedgehog signaling contributes to chemotaxis in cholangiocarcinoma. J Hepatol, 2014, 60(3):599-605.
25. 周良晶, 丁国平, 曹利平, 等.肝门部胆管癌不同分期方法的比较.中华普通外科杂志, 2015, 30(3):177-180.
26. Kentaroh Yamamoto, Fumio Yamamoto, Atsuhiro Maeda, et al. Tubulopapillary adenoma of the gallbladder accompanied by bile duct tumor thrombus. World J Gastroenterol, 2014, 20(26):8736-8739.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions and Significance of Hedgehog Ssignaling Pathway Protein of Ptch1 and Gli1 in Cholangiocarcinoma

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