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, 李緒雄, 舒斌, 等.阻斷Hedgehog信號通路可抑制膽管癌細胞QBC939的生長.中華肝膽外科雜志, 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.	子樹明, 高軍, 楊明, 等.結腸癌中Hedgehog信號轉導通路成員的表達及其意義.中國腫瘤生物治療雜志, 2011, 18(5):539-543.
6.	王偉林, 余翔, 李泉, 等.過表達核心蛋白聚糖基因對膽管癌細胞周期及凋亡的影響.中華實驗外科雜志, 2015, 32(1):69-71.
7.	魏洪亮, 丁志強, 俞亞紅, 等.肝門部膽管癌中Shh和Ptch的表達與腫瘤侵襲性及根治術后復發的關系.華中科技大學學報:醫學版, 2011, 40(2):213-217.
8.	祝珊珊, 李文崗.膽管癌相關信號通路的研究進展.世界華人消化雜志, 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.	虞玲華, 殷新光, 鄔萬新, 等.膽囊癌中Hedgehog信號通路效應蛋白的表達及臨床意義.中華普通外科雜志, 2013, 28(12):968-969.
12.	郭杰芳, 高軍, 李兆申, 等.胰腺癌中GLI1、PTCH1 mRNA的表達及其與臨床指標相關性分析.中華胰腺病雜志, 2010, 10(3):196-198.
13.	余翔, 李泉, 毛永歡, 等.核心蛋白聚糖在膽管癌中的表達及其臨床意義.中華實驗外科雜志, 2014, 31(11):2384-2385.
14.	李曉亮, 肖燎原, 徐志飛, 等.膠質瘤相關癌基因蛋白在腫瘤發生中的作用.現代生物醫學進展, 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, 許小亞, 等.肝門部膽管癌神經浸潤的病理學分析及臨床意義探討.中國普外基礎與臨床雜志, 2015, 22(2):212-215.
19.	劉民鋒, 羅劍, 余險峰, 等. PTEN和mTOR信號轉導通路在膽管癌發展中作用的研究.中國普通外科雜志, 2006, 15(4):274-276.
20.	胡驍, 胡維昱, 孫傳東, 等.肝門部膽管癌根治性切除術后并發癥的診斷和治療.中國現代普通外科進展, 2015, 18(4):328-330.
21.	盛濤, 趙國剛, 徐建, 等. 150例肝外膽管癌的臨床病理與預后分析.河北醫學, 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, 丁國平, 曹利平, 等.肝門部膽管癌不同分期方法的比較.中華普通外科雜志, 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, 李緒雄, 舒斌, 等.阻斷Hedgehog信號通路可抑制膽管癌細胞QBC939的生長.中華肝膽外科雜志, 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. 子樹明, 高軍, 楊明, 等.結腸癌中Hedgehog信號轉導通路成員的表達及其意義.中國腫瘤生物治療雜志, 2011, 18(5):539-543.
6. 王偉林, 余翔, 李泉, 等.過表達核心蛋白聚糖基因對膽管癌細胞周期及凋亡的影響.中華實驗外科雜志, 2015, 32(1):69-71.
7. 魏洪亮, 丁志強, 俞亞紅, 等.肝門部膽管癌中Shh和Ptch的表達與腫瘤侵襲性及根治術后復發的關系.華中科技大學學報:醫學版, 2011, 40(2):213-217.
8. 祝珊珊, 李文崗.膽管癌相關信號通路的研究進展.世界華人消化雜志, 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. 虞玲華, 殷新光, 鄔萬新, 等.膽囊癌中Hedgehog信號通路效應蛋白的表達及臨床意義.中華普通外科雜志, 2013, 28(12):968-969.
12. 郭杰芳, 高軍, 李兆申, 等.胰腺癌中GLI1、PTCH1 mRNA的表達及其與臨床指標相關性分析.中華胰腺病雜志, 2010, 10(3):196-198.
13. 余翔, 李泉, 毛永歡, 等.核心蛋白聚糖在膽管癌中的表達及其臨床意義.中華實驗外科雜志, 2014, 31(11):2384-2385.
14. 李曉亮, 肖燎原, 徐志飛, 等.膠質瘤相關癌基因蛋白在腫瘤發生中的作用.現代生物醫學進展, 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, 許小亞, 等.肝門部膽管癌神經浸潤的病理學分析及臨床意義探討.中國普外基礎與臨床雜志, 2015, 22(2):212-215.
19. 劉民鋒, 羅劍, 余險峰, 等. PTEN和mTOR信號轉導通路在膽管癌發展中作用的研究.中國普通外科雜志, 2006, 15(4):274-276.
20. 胡驍, 胡維昱, 孫傳東, 等.肝門部膽管癌根治性切除術后并發癥的診斷和治療.中國現代普通外科進展, 2015, 18(4):328-330.
21. 盛濤, 趙國剛, 徐建, 等. 150例肝外膽管癌的臨床病理與預后分析.河北醫學, 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, 丁國平, 曹利平, 等.肝門部膽管癌不同分期方法的比較.中華普通外科雜志, 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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