Analysis of Ubiquitin-Specific Protease 9X Expression in Pancreatic Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHANGPeng-bo , DINGWei-chao , ZHANGXiu-zhong , ZHANGChong ,  RENZe-qiang

Department of General Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China;

Corresponding?author：

RENZe-qiang, Email: rzq0805@189.cn

Keywords：

Pancreatic cancer; Ubiquitin-specific protease 9x; Immunohistochemical method; Prognosis

DOI：

10.7507/1007-9424.20150157

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the expression of ubiquitin-specific protease 9X (USP9X) in pancreatic cancer, and to evaluate the correlation of USP9X with the survival of patients with pancreatic cancer. Method The expression of USP9X was detected in 55 pieces of surgically resected primary pancreatic cancer tissues and adjacent nontumorous pancreatic tissues by streptavidin-perosidase immunohistochemical method. Results The rate of USP9X high expression in the 55 pieces of the primary pancreatic cancer tissues was 58.2% (32/55), which in the adjacent nontumorous pancreatic tissues was zero. The expression of USP9X was not correlated with the gender, age, tumor position, or tumor size (P > 0.05), while which was significantly correlated with the differentiation degree, lymph node metastasis, or TNM stage (P < 0.05). By using Cox proportional hazard model, the multivariable analysis revealed that the differentiation degree, lymph node metastasis, and USP9X expression were the independent risk factors. Survival of the patient with USP9X high expression was significantly shorter than that with USP9X low expression (P < 0.05), and there was the same result in the patients with stageⅡ, with lymph node negative, or intermediate differentiation degree (P < 0.05). Conclusion The results indicate that USP9X might play an important role in the pathogenesis and prognosis of pancreatic cancer.

Citation： ZHANGPeng-bo, DINGWei-chao, ZHANGXiu-zhong, ZHANGChong, RENZe-qiang. Analysis of Ubiquitin-Specific Protease 9X Expression in Pancreatic Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(5): 601-604. doi: 10.7507/1007-9424.20150157 Copy

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2.	丁偉超, 張蓬波, 張秀忠, 等.胰腺癌組織中survivin的表達及與預后的關系.中國普通外科雜志, 2014, 23(3):329-332.
3.	楊波, 謝叢華.泛素特異性蛋白酶9X與腫瘤.國際腫瘤學雜志, 2011, 38(12):900-902.
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5.	Peng J, Hu Q, Liu WP, et al. USP9X expression correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma. Diagn Pathol, 2013, 8(1):177-185.
6.	王素霞, 劉媛, 吳慧娟, 等.去泛素化酶的研究及其進展.臨床與實驗病理學雜志, 2008, 24(6):734-737.
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11.	特日格勒, 孫文靖, 于旸, 等.泛素特異性蛋白酶與腫瘤關系的研究.國際遺傳學雜志, 2013, 36(4):162-167.
12.	Burger AM, Seth AK. The ubiquitin-mediated protein degradation pathway in cancer:therapeutic implications. Eur J Cancer, 2004, 40(15):2217-2229.
13.	Pal A, Young MA, Donato NJ. Emerging potential of therapeutic targeting of ubiquitin-specific proteases in the treatment of cancer. Cancer Res, 2014, 74(18):4955-4966.
14.	Reyes-Turcu FE, Wilkinson KD. Polyubiquitin binding and disassembly by deubiquitinating enzymes. Chem Rev, 2009, 109(4):1495-1508.
15.	Agrawal P, Chen YT, Schilling B, et al. Ubiquitin-specific peptidase 9, X-linked (USP9X) modulates activity of mammalian target of rapamycin (mTOR). J Biol Chem, 2012, 287(25):21164-21175.
16.	Populo H, Lopes JM, Soares P. The mTOR signalling pathway in human cancer. Int J Mol Sci, 2012, 13(2):1886-1918.
17.	Schwickart M, Huang X, Lill JR, et al. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature, 2010, 463(7277):103-107.
18.	Nagai H, Noguchi T, Homma K, et al. Ubiquitin-like sequence in ASKl plays critical roles in the recognition and stabilization by USP9X and oxidative stress-induced cell death. Mol Cell, 2009, 36(5):805-818.
19.	魏本尊, 李捷, 沈超, 等.去泛素化酶USP9X在etoposide促結腸癌細胞SW620凋亡中的作用研究.中國現代普通外科進展, 2014, 17(1):8-11, 68.
20.	Trivigno D, Essmann F, Huber SM, et al. Deubiquitinase USP9x confers radioresistance through stabilization of Mcl-1. Neoplasia, 2012, 14(10):893-904.
21.	Harris DR, Mims A, Bunz F. Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil. Cancer Biol Ther, 2012, 13(13):1319-1324.
22.	胡靜, 謝叢華.去泛素化酶USP9X對膠質瘤細胞U251放射敏感性的影響.武漢大學學報:醫學版, 2013, 34(2):213-216.
23.	許娟娟, 劉詩, 易粹瓊.胰腺癌的研究進展.臨床消化病雜志, 2012, 24(2):117-120.
24.	張建宇, 杜云翔, 劉永新, 等.介入化療聯合伽瑪刀治療胰腺癌27例臨床分析.徐州醫學院學報, 2013, 33(7):473-475.
25.	姚汝鋮, 鄭軍, 邢榮春.微小RNA在胰腺癌中的研究進展.中國普外基礎與臨床雜志, 2012, 19(8):911-915.

1. 劉海林, 王磊.胰腺癌早期診斷與治療的研究進展.世界華人消化雜志, 2009, 17(34):3475-3479.
2. 丁偉超, 張蓬波, 張秀忠, 等.胰腺癌組織中survivin的表達及與預后的關系.中國普通外科雜志, 2014, 23(3):329-332.
3. 楊波, 謝叢華.泛素特異性蛋白酶9X與腫瘤.國際腫瘤學雜志, 2011, 38(12):900-902.
4. 成東華.胰腺癌的TNM分期.中國實用外科雜志, 2004, 24(5):67.
5. Peng J, Hu Q, Liu WP, et al. USP9X expression correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma. Diagn Pathol, 2013, 8(1):177-185.
6. 王素霞, 劉媛, 吳慧娟, 等.去泛素化酶的研究及其進展.臨床與實驗病理學雜志, 2008, 24(6):734-737.
7. 戴陳新, 袁健, 鄭亞新.去泛素化酶與腫瘤發生及發展關系的研究進展.中國癌癥雜志, 2013, 23(7):547-550.
8. Crosas B. Deubiquitinating enzyme inhibitors and their potential in cancer therapy. Curr Cancer Drug Targets, 2014, 14(6):506-516.
9. Fraile JM, Quesada V, Rodriguez D, et al. Deubiquitinases in cancer:new functions and therapeutic options. Oncogene, 2012, 31(19):2373-2388.
10. 姚閃, 陳松, 葉茂.去泛素化酶USP7在細胞中的功能作用及其研究進展.激光生物學報, 2014, 23(1):9-15.
11. 特日格勒, 孫文靖, 于旸, 等.泛素特異性蛋白酶與腫瘤關系的研究.國際遺傳學雜志, 2013, 36(4):162-167.
12. Burger AM, Seth AK. The ubiquitin-mediated protein degradation pathway in cancer:therapeutic implications. Eur J Cancer, 2004, 40(15):2217-2229.
13. Pal A, Young MA, Donato NJ. Emerging potential of therapeutic targeting of ubiquitin-specific proteases in the treatment of cancer. Cancer Res, 2014, 74(18):4955-4966.
14. Reyes-Turcu FE, Wilkinson KD. Polyubiquitin binding and disassembly by deubiquitinating enzymes. Chem Rev, 2009, 109(4):1495-1508.
15. Agrawal P, Chen YT, Schilling B, et al. Ubiquitin-specific peptidase 9, X-linked (USP9X) modulates activity of mammalian target of rapamycin (mTOR). J Biol Chem, 2012, 287(25):21164-21175.
16. Populo H, Lopes JM, Soares P. The mTOR signalling pathway in human cancer. Int J Mol Sci, 2012, 13(2):1886-1918.
17. Schwickart M, Huang X, Lill JR, et al. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature, 2010, 463(7277):103-107.
18. Nagai H, Noguchi T, Homma K, et al. Ubiquitin-like sequence in ASKl plays critical roles in the recognition and stabilization by USP9X and oxidative stress-induced cell death. Mol Cell, 2009, 36(5):805-818.
19. 魏本尊, 李捷, 沈超, 等.去泛素化酶USP9X在etoposide促結腸癌細胞SW620凋亡中的作用研究.中國現代普通外科進展, 2014, 17(1):8-11, 68.
20. Trivigno D, Essmann F, Huber SM, et al. Deubiquitinase USP9x confers radioresistance through stabilization of Mcl-1. Neoplasia, 2012, 14(10):893-904.
21. Harris DR, Mims A, Bunz F. Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil. Cancer Biol Ther, 2012, 13(13):1319-1324.
22. 胡靜, 謝叢華.去泛素化酶USP9X對膠質瘤細胞U251放射敏感性的影響.武漢大學學報:醫學版, 2013, 34(2):213-216.
23. 許娟娟, 劉詩, 易粹瓊.胰腺癌的研究進展.臨床消化病雜志, 2012, 24(2):117-120.
24. 張建宇, 杜云翔, 劉永新, 等.介入化療聯合伽瑪刀治療胰腺癌27例臨床分析.徐州醫學院學報, 2013, 33(7):473-475.
25. 姚汝鋮, 鄭軍, 邢榮春.微小RNA在胰腺癌中的研究進展.中國普外基礎與臨床雜志, 2012, 19(8):911-915.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Analysis of Ubiquitin-Specific Protease 9X Expression in Pancreatic Cancer

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