Study on The Relationship Between Expression of Aurka and Clinicopathological Characteristics of Gastric Cancer Patients_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 XUXiu-lian ^1,2 , XIAOJiang-wei ^1,2 , WEIShou-jiang ^1,2 , XIEXian-yong ³ , HUANGYi-fan ³ , TIANXiao-bing ⁴ ,  WANGChong-shu ^1,2

1. The First Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China;
2. Courage Pancreatic Bowel Disease Institute, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China;
3. Department of Pathology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China;
4. Clinical College, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China;

Corresponding author：

WANGChong-shu, Email: chongs-wang@163.com

Keywords：

Aurka; Gastric cancer; Adjacent tissue; Clinicopathological characteristic

DOI：

10.7507/1007-9424.20160371

Video：

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Objective To investigate the expressions of Aurka mRNA and its protein in gastric cancer and adjacent tissues, and to analyzed the relationship between the expression level of Aurka mRAN and clinicopathological characteristics of gastric cancer patients. Methods Retrospectively collected the gastric cancer and adjacent tissues of 198 gastric cancer patients who treated in the Affiliated Hospital of North Sichuan Medical College between April 2011 and September 2013. Using real time quantitative reverse transcription polymerase chain reaction (RT-PCR) method and immunohisto-chemical staining to detected expressions of Aurka mRNA and its protein of gastric cancer and adjacent tissues respectively. At the same time explored the relationship between expression level of Aurka mRNA in gastric cancer tissues and the clinico-pathological features of gastric cancer patients. Results RT-PCR results showed that, the expression level of Aurka mRNA in gastric cancer tissues was 16.62±1.85, which was significantly higher than that of adjacent tissues (7.10±1.59), P < 0.05. Immunohistochemistry results showed that, the positive rate of Aurka protein in gastric cancer tissues was obviously higher than of adjacent tissues[93.9% (186/198) vs. 16.2% (32/198), P < 0.01]. The expression level of Aurka mRNA in gastric cancer tissues was significantly related with a part of the clinicopathological parameters, including TNM staging, T staging, N staging, and differentiation (P < 0.05), but there was no relationship with gender, age, location, and carcino-embryonic antigen (CEA)/CA19-9 level in peripheral blood (P > 0.05). The expression level of Aurka mRNA in Helicobacter pylori (HP)-positive gastric cancer patients was higher than that of HP-negative gastric cancer patients (15.38±1.73 vs. 7.20±1.86, t=-3.74, P < 0.01). Conclusion Expression levels of Aurka gene and its protein were both significantly higher in gastric cancer tissues than those of adjacent tissues, which suggests that Aurka might play a significant role in the procession of the formation and development of gastric cancer as an oncogene, it also suggests that Aurka can be used as a predictor of prognosis and recurrence of patients with gastric cancer.

Citation： XUXiu-lian, XIAOJiang-wei, WEIShou-jiang, XIEXian-yong, HUANGYi-fan, TIANXiao-bing, WANGChong-shu. Study on The Relationship Between Expression of Aurka and Clinicopathological Characteristics of Gastric Cancer Patients. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(12): 1464-1469. doi: 10.7507/1007-9424.20160371 Copy

1.	Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer, 2001, 37 Suppl 8:S4-S66.
2.	赫捷, 赵平, 陈万青, 等. 2011中国肿瘤登记年报.北京:军事医学科学出版社, 2012:1-12.
3.	徐秀连, 王崇树. Maspin、iNOS及VEGF与胃癌关系的研究现状.肿瘤预防与治疗, 2013, 26(2):107-111.
4.	王峰, 时林森, 汪灏, 等. Gastrokine 2在胃癌中的表达及临床意义.中华临床医师杂志:电子版, 2013, 7(20):9037-9041.
5.	Marumoto T, Zhang D, Saya H. Aurora-A--a guardian of poles. Nat Rev Cancer, 2005, 5(1):42-50.
6.	Zhou H, Kuang J, Zhong L, et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet, 1998, 20(2):189-193.
7.	Gritsko TM, Coppola D, Paciga JE, et al. Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res, 2003, 9(4):1420-1426.
8.	Tanaka E, Hashimoto Y, Ito T, et al. The clinical significance of Aurora-A/STK15/BTAK expression in human esophageal squamous cell carcinoma. Clin Cancer Res, 2005, 11(5):1827-1834.
9.	Mesic A, Rogar M, Hudler P, et al. Association of the AURKA and AURKC gene polymorphisms with an increased risk of gastric cancer. IUBMB Life, 2016, 68(8):634-644.
10.	Sehdev V, Katsha A, Arras J, et al. HDM2 regulation by AURKA promotes cell survival in gastric cancer. Clin Cancer Res, 2014, 20(1):76-86.
11.	Katsha A, Soutto M, Sehdev V, et al. Aurora kinase A promotes inflammation and tumorigenesis in mice and human gastric neoplasia. Gastroenterology, 2013, 145(6):1312-1322.
12.	Bischoff JR, Anderson L, Zhu Y, et al. A homologue of drosophila Aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J, 1998, 17(11):3052-3065.
13.	NCCN. NCCN clinical practice guidelines in oncology gastric cancer (including cancer in the proximal 5 cm of the stomach). http://www.nccn.org/professionals/physi-cian_gls/pdf/gastric.
14.	李晓波, 刘文忠.幽门螺杆菌常用诊断方法的评价.中华消化杂志, 2002, 22(11):691-693.
15.	Stojković ML, Durutović DR, Petrović MN, et al. Helicobacter pylori infection in various groups of patients studied, estimated by ¹⁴C-urea breath test. Acta Chir Iugosl, 2011, 58(1):95-98.
16.	陈佳慧, 王崇树. Gastrokine 1在胃癌中的表达变化及其临床病理相关性研究.南充:川北医学院, 2012.
17.	Dar AA, Zaika A, Piazuelo MB, et al. Frequent overexpression of Aurora kinase A in upper gastrointestinal adenocarcinornas correlates with potent antiapoptotic functions. Cancer, 2008, 112(8):1688-1698.
18.	Bolanos-Garcia VM. Aurora kinases. Int J Biochem Cell Biol, 2005, 37(8):1572-1577.
19.	Sugimoto K, Urano T, Zushi H, et al. Molecular dynamics of Aurora-A kinase in living mitotic cells simultaneously visualized with histone H3 and nuclear membrane protein importinalpha. Cell Struct Funct, 2002, 27(6):457-467.
20.	许琳, 王国丽, 戴维亚, 等. Aurora激酶A、B在小鼠受精卵第一次有丝分裂进程中的表达与定位.生殖与避孕, 2011, 31(4):217-225.
21.	Roghi C, Giet R, Uzbekov R, et al. The xenopus protein kinase pEg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules and is involved in bipolar mitotic spindle assembly. J Cell Sci, 1998, 111(Pt 5):557-572.
22.	李强, 吴燕华, 闫晓梅, 等.极光(aurora)激酶在细胞有丝分裂和肿瘤形成中的重要功能.生命科学, 2005, 17(5):424-432.
23.	Warner SL, Bearss DJ, Han H, et al. Targeting aurora-2 kinase in cancer. Mol Cancer Ther, 2003, 2(6):589-595.
24.	Keen N, Taylor S. Aurora-kinase inhibitors as anticancer agents. Nat Rev Cancer, 2004, 4(12):927-936.
25.	Sen S, Zhou H, White RA. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene, 1997, 14(18):2195-2200.
26.	Hartwell LH, Kastan MB. Cell cycle control and cancer. Science, 1994, 266(5192):1821-1828.
27.	Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med, 2004, 10(8):789-799.
28.	Meraldi P, Honda R, Nigg EA. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/-cells. EMBO J, 2002, 21(4):483-492.
29.	Anand S, Penrhyn-Lowe S, Venkitaraman AR. AURORA-A amplifi-cation overrides the mitotic spindle assembly checkpoint, inducing resistance to taxol. Cancer Cell, 2003, 3(1):51-62.
30.	Liu X, Li Z, Song Y, et al. AURKA induces EMT by regulating histone modification through Wnt/β-catenin and PI3K/Akt signaling pathway in gastric cancer. Oncotarget, 2016, 7(22):33152-33164.
31.	Rugge M, Fassan M, Zaninotto G, et al. Aurora kinase A in Barrett's carcinogenesis. Hum Pathol, 2010, 41(10):1380-1386.
32.	吴在德, 吴肇汉, 郑树, 等.外科学.北京:人民卫生出版社, 2004:221-221.
33.	徐秀连. Aurka、LGR5以及SDF-1在胃癌中的表达变化及其临床病理相关性的研究.南充:川北医学院, 2013.
34.	Gisbert JP. Helicobacter pylori-related diseases:dyspepsia, ulcers and gastric cancer. Gastroenterol Hepatol, 2011, 34(Suppl 2):15-26.
35.	张启瑜.钱礼腹部外科学.北京:人民卫生出版社, 2006:157-161.
36.	Weck MN, Gao L, Brenner H. Helicobacter pylori infection and chronic atrophic gastritis:associations according to severity of disease. Epidemiology, 2009, 20(4):569-574.
37.	Ohata H, Kitauchi S, Yoshimura N, et al. Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer, 2004, 109(1):138-143.

1. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer, 2001, 37 Suppl 8:S4-S66.
2. 赫捷, 赵平, 陈万青, 等. 2011中国肿瘤登记年报.北京:军事医学科学出版社, 2012:1-12.
3. 徐秀连, 王崇树. Maspin、iNOS及VEGF与胃癌关系的研究现状.肿瘤预防与治疗, 2013, 26(2):107-111.
4. 王峰, 时林森, 汪灏, 等. Gastrokine 2在胃癌中的表达及临床意义.中华临床医师杂志:电子版, 2013, 7(20):9037-9041.
5. Marumoto T, Zhang D, Saya H. Aurora-A--a guardian of poles. Nat Rev Cancer, 2005, 5(1):42-50.
6. Zhou H, Kuang J, Zhong L, et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet, 1998, 20(2):189-193.
7. Gritsko TM, Coppola D, Paciga JE, et al. Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res, 2003, 9(4):1420-1426.
8. Tanaka E, Hashimoto Y, Ito T, et al. The clinical significance of Aurora-A/STK15/BTAK expression in human esophageal squamous cell carcinoma. Clin Cancer Res, 2005, 11(5):1827-1834.
9. Mesic A, Rogar M, Hudler P, et al. Association of the AURKA and AURKC gene polymorphisms with an increased risk of gastric cancer. IUBMB Life, 2016, 68(8):634-644.
10. Sehdev V, Katsha A, Arras J, et al. HDM2 regulation by AURKA promotes cell survival in gastric cancer. Clin Cancer Res, 2014, 20(1):76-86.
11. Katsha A, Soutto M, Sehdev V, et al. Aurora kinase A promotes inflammation and tumorigenesis in mice and human gastric neoplasia. Gastroenterology, 2013, 145(6):1312-1322.
12. Bischoff JR, Anderson L, Zhu Y, et al. A homologue of drosophila Aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J, 1998, 17(11):3052-3065.
13. NCCN. NCCN clinical practice guidelines in oncology gastric cancer (including cancer in the proximal 5 cm of the stomach). http://www.nccn.org/professionals/physi-cian_gls/pdf/gastric.
14. 李晓波, 刘文忠.幽门螺杆菌常用诊断方法的评价.中华消化杂志, 2002, 22(11):691-693.
15. Stojković ML, Durutović DR, Petrović MN, et al. Helicobacter pylori infection in various groups of patients studied, estimated by ¹⁴C-urea breath test. Acta Chir Iugosl, 2011, 58(1):95-98.
16. 陈佳慧, 王崇树. Gastrokine 1在胃癌中的表达变化及其临床病理相关性研究.南充:川北医学院, 2012.
17. Dar AA, Zaika A, Piazuelo MB, et al. Frequent overexpression of Aurora kinase A in upper gastrointestinal adenocarcinornas correlates with potent antiapoptotic functions. Cancer, 2008, 112(8):1688-1698.
18. Bolanos-Garcia VM. Aurora kinases. Int J Biochem Cell Biol, 2005, 37(8):1572-1577.
19. Sugimoto K, Urano T, Zushi H, et al. Molecular dynamics of Aurora-A kinase in living mitotic cells simultaneously visualized with histone H3 and nuclear membrane protein importinalpha. Cell Struct Funct, 2002, 27(6):457-467.
20. 许琳, 王国丽, 戴维亚, 等. Aurora激酶A、B在小鼠受精卵第一次有丝分裂进程中的表达与定位.生殖与避孕, 2011, 31(4):217-225.
21. Roghi C, Giet R, Uzbekov R, et al. The xenopus protein kinase pEg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules and is involved in bipolar mitotic spindle assembly. J Cell Sci, 1998, 111(Pt 5):557-572.
22. 李强, 吴燕华, 闫晓梅, 等.极光(aurora)激酶在细胞有丝分裂和肿瘤形成中的重要功能.生命科学, 2005, 17(5):424-432.
23. Warner SL, Bearss DJ, Han H, et al. Targeting aurora-2 kinase in cancer. Mol Cancer Ther, 2003, 2(6):589-595.
24. Keen N, Taylor S. Aurora-kinase inhibitors as anticancer agents. Nat Rev Cancer, 2004, 4(12):927-936.
25. Sen S, Zhou H, White RA. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene, 1997, 14(18):2195-2200.
26. Hartwell LH, Kastan MB. Cell cycle control and cancer. Science, 1994, 266(5192):1821-1828.
27. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med, 2004, 10(8):789-799.
28. Meraldi P, Honda R, Nigg EA. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/-cells. EMBO J, 2002, 21(4):483-492.
29. Anand S, Penrhyn-Lowe S, Venkitaraman AR. AURORA-A amplifi-cation overrides the mitotic spindle assembly checkpoint, inducing resistance to taxol. Cancer Cell, 2003, 3(1):51-62.
30. Liu X, Li Z, Song Y, et al. AURKA induces EMT by regulating histone modification through Wnt/β-catenin and PI3K/Akt signaling pathway in gastric cancer. Oncotarget, 2016, 7(22):33152-33164.
31. Rugge M, Fassan M, Zaninotto G, et al. Aurora kinase A in Barrett's carcinogenesis. Hum Pathol, 2010, 41(10):1380-1386.
32. 吴在德, 吴肇汉, 郑树, 等.外科学.北京:人民卫生出版社, 2004:221-221.
33. 徐秀连. Aurka、LGR5以及SDF-1在胃癌中的表达变化及其临床病理相关性的研究.南充:川北医学院, 2013.
34. Gisbert JP. Helicobacter pylori-related diseases:dyspepsia, ulcers and gastric cancer. Gastroenterol Hepatol, 2011, 34(Suppl 2):15-26.
35. 张启瑜.钱礼腹部外科学.北京:人民卫生出版社, 2006:157-161.
36. Weck MN, Gao L, Brenner H. Helicobacter pylori infection and chronic atrophic gastritis:associations according to severity of disease. Epidemiology, 2009, 20(4):569-574.
37. Ohata H, Kitauchi S, Yoshimura N, et al. Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer, 2004, 109(1):138-143.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study on The Relationship Between Expression of Aurka and Clinicopathological Characteristics of Gastric Cancer Patients

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