Expressions and clinical significance of Notch-2 protein and Numb protein in papillary thyroid carcinoma tissues_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YANG Fuqiang ^1,2 , WANG Yan ^1,2 , MA Jingyou ^1,2 , LI Zheng ¹ ,  LIU Zhen ^1,2

1. The Clinical College, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia Autonomous Rigon 028000, P. R. China;
2. Department of General Surgery, The Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia Autonomous Rigon 028000, P. R. China;

Corresponding author：

LIU Zhen, Email: liuzhen95@sohu.com

Keywords：

papillary thyroid carcinoma; Notch-2 protein; Numb protein; immunohistochemistry

DOI：

10.7507/1007-9424.201707059

Video：

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Objective To investigate the expressions and clinical significance of Notch-2 protein and Numb protein in papillary thyroid carcinoma (PTC). Methods PTC tissues and its para-cancerous tissues of 50 patients with PTC who treated in The Affiliated Hospital of Inner Mongolia University for Nationalities from Mar. 2014 to Mar. 2017 were retrospectively collectied, to detect the expressions of Notch-2 protein and Numb protein by immunohistochenmical method. Results ① Expressions of Notch-2 protein and Numb protein in PTC tissues and para-cancerous tissues: the positive-expression rate of Notch-2 protein in PTC tissues was 82.00% (41/50), which was higher than that of para-cancerous tissues〔18.00% (9/50)〕, the difference was statistically significant (χ²=40.960, P<0.001). The positive-expression rate of Numb protein in PTC tissues was 66.00% (33/50), which was higher than that of para-cancerous tissues 〔0 (0/50) 〕, the difference was statistically significant (χ²=49.254, P<0.001). ② The relationship between expression of Notch-2 protein and expression of Numb protein in PTC tissues: there was a positive correlation between expressions of Notch-2 protein and Numb protein in PTC tissues (r_s=0.323, P=0.022). ③ The relationship between expressions of Notch-2 protein and Numb protein in PTC tissues and clinicopathological features of the PTC patients: the expression of Notch-2 protein in PTC tissues was not significantly correlated with gender, age, tumor diameter, capsule infiltration, cervical lymph node metastasis, and TNM staging (P>0.05). The expression of Numb protein in PTC tissues was not significantly correlated with gender, age, tumor diameter, and capsule infiltration (P>0.05), but was significantly correlated with cervical lymph node metastasis and TNM staging (P<0.05), the positive rates of Numb protein in patients of staging Ⅲ+Ⅳ group and cervical lymph node metastasis group were lower than those of patients in staging Ⅰ+Ⅱ group and non-cervical lymph node metastasis group. Conclusion The positive-expression rate of Notch-2 protein and Numb protein in PTC tissues are higher than those of para-cancerous tissues, and there is a positive correlation between them in PTC tissues, suggesting that there may be a synergistic effect in the course of PTC progression.

Citation： YANG Fuqiang, WANG Yan, MA Jingyou, LI Zheng, LIU Zhen. Expressions and clinical significance of Notch-2 protein and Numb protein in papillary thyroid carcinoma tissues. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(1): 59-64. doi: 10.7507/1007-9424.201707059 Copy

1.	吴孟超, 吴在德. 黄家驷外科学. 北京: 人民卫生出版社, 2008: 1136-1139.
2.	陈孝平, 汪建平. 外科学. 第 8 版. 北京: 人民卫生出版社, 2013: 237-249.
3.	马竞优, 崔喆旭, 李华根, 等. Notch-1 在乳头状甲状腺癌和颈部转移淋巴结中的表达和临床意义. 中国普外基础与临床杂志, 2017, 24(1): 70-73.
4.	曾令瑞, 韩玉贞, 马英路, 等. 乳腺原发癌和相应淋巴结转移癌干细胞 Wnt、Notch 信号通路相关分子的比较. 临床与实验病理学杂志, 2014, 30(9): 963-966.
5.	俞谦, 邵喜明, 李华顺. NUMB 调控肿瘤增殖的机制研究. 四川大学学报 (医学版), 2014, 45(5): 744-748.
6.	Guo LY, Li YM, Qiao L, et al. Notch2 regulates matrix metallopeptidase 9 via PI3K/AKT signaling in human gastric carcinoma cell MKN-45. World J Gastroenterol, 2012, 18(48): 7262-7270.
7.	Brown LM, Helmke SM, Hunsucker SW, et al. Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue. Mol Carcinog, 2006, 45(8): 613-626.
8.	An H, Ge W, Xi Y, et al. Inscuteable maintains type I neuroblast lineage identity via Numb/Notch signaling in the Drosophila larval brain. J Genet Genomics, 2017, 44(3): 151-162.
9.	Zhang M, Qin Y, Zuo B, et al. Overexpression of NOTCH-regulated Ankyrin Repeat Protein is associated with papillary thyroid carcinoma progression. PLoS One, 2017, 12(2): e0167782.
10.	康艳. 甲状腺乳头状癌组织中 Numb 与 p53 蛋白的表达及临床意义. 长春: 吉林大学, 2013.
11.	曹子龙, 张卓, 胡建立, 等. NKD1 和 APC 在乳腺癌组织中的表达及意义. 中国普外基础与临床杂志, 2015, 22(10): 1226-1229.
12.	Yu J, Mai W, Cui Y, et al. Key genes and pathways predicted in papillary thyroid carcinoma based on bioinformatics analysis. J Endocrinol Invest, 2016, 39(11): 1285-1293.
13.	Jung CW, Kong JS, Seol H, et al.Expression of activated Notch1 and Hey1 in papillary thyroid carcinoma. Histopathology, 2017, 70(2): 301-308.
14.	Kim WB. A closer look at papillary thyroid carcinoma. Endocrinol Metab (Seoul), 2015, 30(1): 1-6.
15.	Rennstam K, McMichael N, Berglund P, et al. Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer. Breast Cancer Res Treat, 2010, 122(2): 315-324.
16.	谢承志, 徐迅迪. Numb 的研究现状及展望. 中国普通外科杂志, 2009, 18(9): 967-971.
17.	张奇, 宋鑫. Notch 信号通路在肿瘤干细胞中的研究进展. 中国肿瘤, 2014, 23(7): 585-590.
18.	邓维叶, 陈艳峰, 郭朱明, 等. 甲状腺乳头状癌 Notch-1 表达及复发相关因素分析. 肿瘤研究与临床, 2015, 27(1): 11-14.
19.	杨晶金, 姚军, 沈峰清, 等. Notch-1 信号通路与甲状腺乳头状癌的关系. 中国细胞生物学学报, 2012, 34(2): 120-126.
20.	龚艳萍, 龚日祥, 杨敬, 等. 甲状腺乳头状癌 BRAF 基因突变与临床病理特征间的关系及临床意义. 四川大学学报 (医学版), 2013, 44(4): 662-665.
21.	Mseddi M, Ben Mansour R, Gouiia N, et al. A comparative study of nuclear 8-hydroxyguanosine expression in Autoimmune Thyroid Diseases and Papillary Thyroid Carcinoma and its relationship with p53, Bcl-2 and Ki-67 cancer related proteins. Adv Med Sci, 2017, 62(1): 45-51.
22.	Côrtes MCS, Rosario PW, Mourão GF, et al. Influence of chronic lymphocytic thyroiditis on the risk of persistent and recurrent disease in patients with papillary thyroid carcinoma and elevated antithyroglobulin antibodies after initial therapy. Braz J Otorhinolaryngol, 2017, [Epub ahead of print].
23.	魏秋芳, 刘良裕, 刘枫, 等. Notch 信号通路与肿瘤干细胞及抑制剂研究进展. 中国药学杂志, 2014, 49(6): 441-448.
24.	李佳, 孙梦黎, 黄健, 等. Notch 信号通路与生殖干细胞研究进展. 中国细胞生物学学报, 2014, 36(6): 841-846.
25.	万健, 唐才喜, 冯斌, 等. 原发性肝癌中 Numb 和 VEGF 的表达及临床意义. 中国普通外科杂志, 2015, 24(1): 39-44.
26.	万伯顺, 陈跃宇, 史佩东, 等. Numb 对结肠癌细胞迁移和侵袭的影响. 肿瘤, 2015, 35(8): 842-848.
27.	张平, 董文武, 崔俊帅, 等. 选择性中央区淋巴结清扫治疗 cN0 甲状腺乳头状癌的临床价值. 中国普外基础与临床杂志, 2014, 21(2): 182-186.
28.	孟晓敏, 温树信, 王斌全, 等. 甲状腺乳头状癌原发灶外科治疗的 Meta 分析. 临床耳鼻咽喉头颈外科杂志, 2015, 29(9): 835-840.

1. 吴孟超, 吴在德. 黄家驷外科学. 北京: 人民卫生出版社, 2008: 1136-1139.
2. 陈孝平, 汪建平. 外科学. 第 8 版. 北京: 人民卫生出版社, 2013: 237-249.
3. 马竞优, 崔喆旭, 李华根, 等. Notch-1 在乳头状甲状腺癌和颈部转移淋巴结中的表达和临床意义. 中国普外基础与临床杂志, 2017, 24(1): 70-73.
4. 曾令瑞, 韩玉贞, 马英路, 等. 乳腺原发癌和相应淋巴结转移癌干细胞 Wnt、Notch 信号通路相关分子的比较. 临床与实验病理学杂志, 2014, 30(9): 963-966.
5. 俞谦, 邵喜明, 李华顺. NUMB 调控肿瘤增殖的机制研究. 四川大学学报 (医学版), 2014, 45(5): 744-748.
6. Guo LY, Li YM, Qiao L, et al. Notch2 regulates matrix metallopeptidase 9 via PI3K/AKT signaling in human gastric carcinoma cell MKN-45. World J Gastroenterol, 2012, 18(48): 7262-7270.
7. Brown LM, Helmke SM, Hunsucker SW, et al. Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue. Mol Carcinog, 2006, 45(8): 613-626.
8. An H, Ge W, Xi Y, et al. Inscuteable maintains type I neuroblast lineage identity via Numb/Notch signaling in the Drosophila larval brain. J Genet Genomics, 2017, 44(3): 151-162.
9. Zhang M, Qin Y, Zuo B, et al. Overexpression of NOTCH-regulated Ankyrin Repeat Protein is associated with papillary thyroid carcinoma progression. PLoS One, 2017, 12(2): e0167782.
10. 康艳. 甲状腺乳头状癌组织中 Numb 与 p53 蛋白的表达及临床意义. 长春: 吉林大学, 2013.
11. 曹子龙, 张卓, 胡建立, 等. NKD1 和 APC 在乳腺癌组织中的表达及意义. 中国普外基础与临床杂志, 2015, 22(10): 1226-1229.
12. Yu J, Mai W, Cui Y, et al. Key genes and pathways predicted in papillary thyroid carcinoma based on bioinformatics analysis. J Endocrinol Invest, 2016, 39(11): 1285-1293.
13. Jung CW, Kong JS, Seol H, et al.Expression of activated Notch1 and Hey1 in papillary thyroid carcinoma. Histopathology, 2017, 70(2): 301-308.
14. Kim WB. A closer look at papillary thyroid carcinoma. Endocrinol Metab (Seoul), 2015, 30(1): 1-6.
15. Rennstam K, McMichael N, Berglund P, et al. Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer. Breast Cancer Res Treat, 2010, 122(2): 315-324.
16. 谢承志, 徐迅迪. Numb 的研究现状及展望. 中国普通外科杂志, 2009, 18(9): 967-971.
17. 张奇, 宋鑫. Notch 信号通路在肿瘤干细胞中的研究进展. 中国肿瘤, 2014, 23(7): 585-590.
18. 邓维叶, 陈艳峰, 郭朱明, 等. 甲状腺乳头状癌 Notch-1 表达及复发相关因素分析. 肿瘤研究与临床, 2015, 27(1): 11-14.
19. 杨晶金, 姚军, 沈峰清, 等. Notch-1 信号通路与甲状腺乳头状癌的关系. 中国细胞生物学学报, 2012, 34(2): 120-126.
20. 龚艳萍, 龚日祥, 杨敬, 等. 甲状腺乳头状癌 BRAF 基因突变与临床病理特征间的关系及临床意义. 四川大学学报 (医学版), 2013, 44(4): 662-665.
21. Mseddi M, Ben Mansour R, Gouiia N, et al. A comparative study of nuclear 8-hydroxyguanosine expression in Autoimmune Thyroid Diseases and Papillary Thyroid Carcinoma and its relationship with p53, Bcl-2 and Ki-67 cancer related proteins. Adv Med Sci, 2017, 62(1): 45-51.
22. Côrtes MCS, Rosario PW, Mourão GF, et al. Influence of chronic lymphocytic thyroiditis on the risk of persistent and recurrent disease in patients with papillary thyroid carcinoma and elevated antithyroglobulin antibodies after initial therapy. Braz J Otorhinolaryngol, 2017, [Epub ahead of print].
23. 魏秋芳, 刘良裕, 刘枫, 等. Notch 信号通路与肿瘤干细胞及抑制剂研究进展. 中国药学杂志, 2014, 49(6): 441-448.
24. 李佳, 孙梦黎, 黄健, 等. Notch 信号通路与生殖干细胞研究进展. 中国细胞生物学学报, 2014, 36(6): 841-846.
25. 万健, 唐才喜, 冯斌, 等. 原发性肝癌中 Numb 和 VEGF 的表达及临床意义. 中国普通外科杂志, 2015, 24(1): 39-44.
26. 万伯顺, 陈跃宇, 史佩东, 等. Numb 对结肠癌细胞迁移和侵袭的影响. 肿瘤, 2015, 35(8): 842-848.
27. 张平, 董文武, 崔俊帅, 等. 选择性中央区淋巴结清扫治疗 cN0 甲状腺乳头状癌的临床价值. 中国普外基础与临床杂志, 2014, 21(2): 182-186.
28. 孟晓敏, 温树信, 王斌全, 等. 甲状腺乳头状癌原发灶外科治疗的 Meta 分析. 临床耳鼻咽喉头颈外科杂志, 2015, 29(9): 835-840.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions and clinical significance of Notch-2 protein and Numb protein in papillary thyroid carcinoma tissues

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