The relationship between the expression of PTEN/Basigin1 protein and clinicopathological features in breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Jianjun , XU Xiaoyan , FENG Zhikun ,  YANG Jinhua

Department of Pathology, People’s Hospital of Zhengzhou, Zhengzhou 450000, P. R. China;

Corresponding author：

YANG Jinhua, Email: jinhuay65@sina.com

Keywords：

invasive ductal carcinoma of breast; phosphate and tension homology deleted on chromsome ten; Basigin1; clinicopathologic feature; molecular subtype; correlation

DOI：

10.7507/1007-9424.201908115

Video：

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Objective To investigate the expression of phosphate and tension homology deleted on chromsome ten (PTEN) and Basigin1, as well as their relationships with clinicopathological factors and molecular subtypes in invasive ductal carcinoma of breast. Methods The expressions of PTEN and Basigin1 protein were examined in 76 invasive ductal carcinoma of breast tissues by immunohistochemical method, and 20 breast benign hyperplasia tissues as control. These 76 patients underwent surgery in our hospital from Jan. 2014 to Dec. 2015. Results The high-expression rate of PTEN protein in invasive ductal carcinoma of breast tissues was lower than that in benign hyperplasia tissues [56.6% (43/76) vs. 85.0% (17/20), χ²=5.457, P=0.019], while the high-expression rate of Basigin1 protein was higher than that of the benign hyperplasia tissues [51.3% (39/76) vs 25.0% (5/20), χ²=4.417, P=0.036]. The high-expression of PTEN protein was positively correlated with WHO grade and lymph node metastasis status (P<0.05). The high-expression of Basigin1 protein was positively correlated with WHO grade, lymph node metastasis status, and TNM stage (P<0.05). In addition, the high-expression of PTEN protein was associated with molecular subtypes of breast cancer (P<0.001), and its high-expression rate was higher in Luminal A and Luminal B patients; the high-expression of Basigin1 protein was associated with molecular subtypes of breast cancer too (P<0.001), and the high-expression rate of Basigin1 protein was higher in Her-2 overexpression and basal-like subtypes of breast cancer patients. Spearman correlation analysis shown that expression of PTEN protein was negatively correlated with expression of Basigin1 protein (r_s=–0.481, P<0.001). Conclusion PTEN and Basigin1 protein may have some mechanisms to promote the occurrence and development of breast cancer, which provide a new basis for targeted treatment of breast cancer.

Citation： WANG Jianjun, XU Xiaoyan, FENG Zhikun, YANG Jinhua. The relationship between the expression of PTEN/Basigin1 protein and clinicopathological features in breast cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(7): 825-830. doi: 10.7507/1007-9424.201908115 Copy

1.	Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): e279-e289.
2.	Kechagioglou P, Papi RM, Provatopoulou X, et al. Tumor suppressor PTEN in breast cancer: heterozygosity, mutations and protein expression. Anticancer Res, 2014, 34(3): 1387-1400.
3.	张涛, 梅亚男. Ki67、p53和PTEN在乳腺癌中的表达及临床意义. 中国妇幼保健, 2017, 32(13): 2862-2865.
4.	Tian T, Nan KJ, Wang SH, et al. PTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and independent mechanisms in HepG2 cells. Carcinogenesis, 2010, 31(7): 1211-1219.
5.	Noh EM, Kim JM, Hong OY, et al. PTEN inhibits replicative senescence-induced MMP-1 expression by regulating NOX4-mediated ROS in human dermal fibroblasts. J Cell Mol Med, 2017, 21(11): 3113-3116.
6.	Ding P, Zhang X, Jin S, et al. CD147 functions as the signaling receptor for extracellular divalent copper in hepatocellular carcinoma cells. Oncotarget, 2017, 8(31): 51151-51163.
7.	徐小艳, 徐宪伟, 王慧, 等. PTEN和EMMPRIN在肺腺癌组织中的表达及其与EGFR基因突变的关系. 肿瘤防治研究, 2017, (5): 324-328.
8.	李昌秀, 徐红梅, 杨达荣, 等. CD147 PTEN E-钙黏蛋白在食管癌组织中表达与临床病理的关系. 检验医学与临床, 2013, 10(2): 129-131.
9.	王耀东, 孙尚奎, 刘强. 胶质瘤术后组织中Bmi-1、CD147和PTEN的表达及意义. 中国老年学杂志, 2015, 35(8): 2205-2206.
10.	Frank GA, Danilova NV, Andreeva II, et al. WHO Classification of tumors of the breast, 2012. Arkh Patol, 2013, 75(2): 53-63.
11.	Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature, 2012, 490(7418): 61-70.
12.	Yim K, Park HS, Kim DM, et al. Image analysis of HER2 immunohistochemical staining of surgical breast cancer specimens. Yonsei Med J, 2019, 60(2): 158-162.
13.	Ferraz da Costa DC, Campos NPC, Santos RA, et al. Resveratrol prevents p53 aggregation in vitro and in breast cancer cells. Oncotarget, 2018, 9(49): 29112-29122.
14.	Citi V, Del Re M, Martelli A, et al. Phosphorylation of AKT and ERK1/2 and mutations of PIK3CA and PTEN are predictive of breast cancer cell sensitivity to everolimus in vitro. Cancer Chemother Pharmacol, 2018, 81(4): 745-754.
15.	Marsit CJ, Zheng S, Aldape K, et al. PTEN expression in non-small-cell lung cancer: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration. Hum Pathol, 2005, 36(7): 768-776.
16.	Ong CW, Maxwell P, Alvi MA, et al. A gene signature associated with PTEN activation defines good prognosis intermediate risk prostate cancer cases. J Pathol Clin Res, 2018, 4(2): 103-113.
17.	Wu Q, Yu S, Chen J, et al. Downregulation of STRAP promotes tumor growth and metastasis in hepatocellular carcinoma via reducing PTEN level. IUBMB Life, 2018, 70(2): 120-128.
18.	Peng J, Ma W, Zhou Z, et al. Genetic variations in the PI3K/PTEN/AKT/mTOR pathway predict tumor response and disease-free survival in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy and radical surgery. J Cancer, 2018, 9(6): 1067-1077.
19.	Constantinou C, Papadopoulos S, Karyda E, et al. Expression and clinical significance of claudin-7, PDL-1, PTEN, c-Kit, c-Met,c-Myc, ALK, CK5/6, CK17, p53, EGFR, Ki67, p63 in triple-negative breast cancer-a single centre prospective observational study. In Vivo, 2018, 32(2): 303-311.
20.	Hu XX, Xu XN, He BS, et al. microRNA-485-5p functions as a tumor suppressor in colorectal cancer cells by targeting CD147. J Cancer, 2018, 9(15): 2603-2611.
21.	Mori A, Watanabe M, Sadahira T, et al. The downregulation of the expression of CD147 by tumor suppressor REIC/Dkk-3, and its implication in human prostate cancer cell growth inhibition. Acta Med Okayama, 2017, 71(2): 135-142.
22.	周子寒, 余红平. 肿瘤分子病理流行病学. 中国癌症防治杂志, 2018, 10(2): 85-89.
23.	Asgari R, Mansouri K, Bakhtiari M, et al. CD147 as an apoptosis regulator in spermatogenesis: deciphering its association with matrix metalloproteinases’ pathway. Mol Biol Rep, 2019, 46(1): 1099-1105.
24.	Li F, Zhang J, Guo J, et al. RNA interference targeting CD147 inhibits metastasis and invasion of human breast cancer MCF-7 cells by downregulating MMP-9/VEGF expression. Acta Biochim Biophys Sin (Shanghai), 2018, 50(7): 676-684.
25.	Xu X, Liu S, Lei B, et al. Expression of HAb18G in non-small lung cancer and characterization of activation, migration, proliferation, and apoptosis in A549 cells following siRNA-induced downregulation of HAb18G. Mol Cell Biochem, 2013, 383(1-2): 1-11.
26.	Li ZH, Li L, Kang LP, et al. MicroRNA-92a promotes tumor growth and suppresses immune function through activation of MAPK/ERK signaling pathway by inhibiting PTEN in mice bearing U14 cervical cancer. Cancer Med, 2018, 7(7): 3118-3131.
27.	Liu X, Chen Q, Hu XG, et al. PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT. Tumour Biol, 2016, 37(10): 13479-13487.
28.	Ma C, Wang J, Fan L, et al. Inhibition of CD147 expression promotes chemosensitivity in HNSCC cells by deactivating MAPK/ERK signaling pathway. Exp Mol Pathol, 2017, 102(1): 59-64.
29.	Xu T, Zhou M, Peng L, et al. Upregulation of CD147 promotes cell invasion, epithelial-to-mesenchymal transition and activates MAPK/ERK signaling pathway in colorectal cancer. Int J Clin Exp Pathol, 2014, 7(11): 7432-7441.
30.	李杰宝, 喻晓程, 田野. 乳腺癌分子分型与临床病理参数的关系及预后. 中华实验外科杂志, 2018, 35(6): 1027-1029.

1. Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): e279-e289.
2. Kechagioglou P, Papi RM, Provatopoulou X, et al. Tumor suppressor PTEN in breast cancer: heterozygosity, mutations and protein expression. Anticancer Res, 2014, 34(3): 1387-1400.
3. 张涛, 梅亚男. Ki67、p53和PTEN在乳腺癌中的表达及临床意义. 中国妇幼保健, 2017, 32(13): 2862-2865.
4. Tian T, Nan KJ, Wang SH, et al. PTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and independent mechanisms in HepG2 cells. Carcinogenesis, 2010, 31(7): 1211-1219.
5. Noh EM, Kim JM, Hong OY, et al. PTEN inhibits replicative senescence-induced MMP-1 expression by regulating NOX4-mediated ROS in human dermal fibroblasts. J Cell Mol Med, 2017, 21(11): 3113-3116.
6. Ding P, Zhang X, Jin S, et al. CD147 functions as the signaling receptor for extracellular divalent copper in hepatocellular carcinoma cells. Oncotarget, 2017, 8(31): 51151-51163.
7. 徐小艳, 徐宪伟, 王慧, 等. PTEN和EMMPRIN在肺腺癌组织中的表达及其与EGFR基因突变的关系. 肿瘤防治研究, 2017, (5): 324-328.
8. 李昌秀, 徐红梅, 杨达荣, 等. CD147 PTEN E-钙黏蛋白在食管癌组织中表达与临床病理的关系. 检验医学与临床, 2013, 10(2): 129-131.
9. 王耀东, 孙尚奎, 刘强. 胶质瘤术后组织中Bmi-1、CD147和PTEN的表达及意义. 中国老年学杂志, 2015, 35(8): 2205-2206.
10. Frank GA, Danilova NV, Andreeva II, et al. WHO Classification of tumors of the breast, 2012. Arkh Patol, 2013, 75(2): 53-63.
11. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature, 2012, 490(7418): 61-70.
12. Yim K, Park HS, Kim DM, et al. Image analysis of HER2 immunohistochemical staining of surgical breast cancer specimens. Yonsei Med J, 2019, 60(2): 158-162.
13. Ferraz da Costa DC, Campos NPC, Santos RA, et al. Resveratrol prevents p53 aggregation in vitro and in breast cancer cells. Oncotarget, 2018, 9(49): 29112-29122.
14. Citi V, Del Re M, Martelli A, et al. Phosphorylation of AKT and ERK1/2 and mutations of PIK3CA and PTEN are predictive of breast cancer cell sensitivity to everolimus in vitro. Cancer Chemother Pharmacol, 2018, 81(4): 745-754.
15. Marsit CJ, Zheng S, Aldape K, et al. PTEN expression in non-small-cell lung cancer: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration. Hum Pathol, 2005, 36(7): 768-776.
16. Ong CW, Maxwell P, Alvi MA, et al. A gene signature associated with PTEN activation defines good prognosis intermediate risk prostate cancer cases. J Pathol Clin Res, 2018, 4(2): 103-113.
17. Wu Q, Yu S, Chen J, et al. Downregulation of STRAP promotes tumor growth and metastasis in hepatocellular carcinoma via reducing PTEN level. IUBMB Life, 2018, 70(2): 120-128.
18. Peng J, Ma W, Zhou Z, et al. Genetic variations in the PI3K/PTEN/AKT/mTOR pathway predict tumor response and disease-free survival in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy and radical surgery. J Cancer, 2018, 9(6): 1067-1077.
19. Constantinou C, Papadopoulos S, Karyda E, et al. Expression and clinical significance of claudin-7, PDL-1, PTEN, c-Kit, c-Met,c-Myc, ALK, CK5/6, CK17, p53, EGFR, Ki67, p63 in triple-negative breast cancer-a single centre prospective observational study. In Vivo, 2018, 32(2): 303-311.
20. Hu XX, Xu XN, He BS, et al. microRNA-485-5p functions as a tumor suppressor in colorectal cancer cells by targeting CD147. J Cancer, 2018, 9(15): 2603-2611.
21. Mori A, Watanabe M, Sadahira T, et al. The downregulation of the expression of CD147 by tumor suppressor REIC/Dkk-3, and its implication in human prostate cancer cell growth inhibition. Acta Med Okayama, 2017, 71(2): 135-142.
22. 周子寒, 余红平. 肿瘤分子病理流行病学. 中国癌症防治杂志, 2018, 10(2): 85-89.
23. Asgari R, Mansouri K, Bakhtiari M, et al. CD147 as an apoptosis regulator in spermatogenesis: deciphering its association with matrix metalloproteinases’ pathway. Mol Biol Rep, 2019, 46(1): 1099-1105.
24. Li F, Zhang J, Guo J, et al. RNA interference targeting CD147 inhibits metastasis and invasion of human breast cancer MCF-7 cells by downregulating MMP-9/VEGF expression. Acta Biochim Biophys Sin (Shanghai), 2018, 50(7): 676-684.
25. Xu X, Liu S, Lei B, et al. Expression of HAb18G in non-small lung cancer and characterization of activation, migration, proliferation, and apoptosis in A549 cells following siRNA-induced downregulation of HAb18G. Mol Cell Biochem, 2013, 383(1-2): 1-11.
26. Li ZH, Li L, Kang LP, et al. MicroRNA-92a promotes tumor growth and suppresses immune function through activation of MAPK/ERK signaling pathway by inhibiting PTEN in mice bearing U14 cervical cancer. Cancer Med, 2018, 7(7): 3118-3131.
27. Liu X, Chen Q, Hu XG, et al. PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT. Tumour Biol, 2016, 37(10): 13479-13487.
28. Ma C, Wang J, Fan L, et al. Inhibition of CD147 expression promotes chemosensitivity in HNSCC cells by deactivating MAPK/ERK signaling pathway. Exp Mol Pathol, 2017, 102(1): 59-64.
29. Xu T, Zhou M, Peng L, et al. Upregulation of CD147 promotes cell invasion, epithelial-to-mesenchymal transition and activates MAPK/ERK signaling pathway in colorectal cancer. Int J Clin Exp Pathol, 2014, 7(11): 7432-7441.
30. 李杰宝, 喻晓程, 田野. 乳腺癌分子分型与临床病理参数的关系及预后. 中华实验外科杂志, 2018, 35(6): 1027-1029.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The relationship between the expression of PTEN/Basigin1 protein and clinicopathological features in breast cancer

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