Expression of PTEN and EMMPRIN in Lung Adenocarcinoma Tissues and Their Correlation with EGFR Mutation
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摘要:目的
观察肺腺癌中PTEN和EMMPRIN蛋白水平的表达，分析其与肺腺癌临床病理特征及EGFR基因突变的关系。
方法选取10例正常肺组织作为对照组，分别用免疫组织化学法和PCR法检测90例肺腺癌组织中PTEN和EMMPRIN蛋白的表达和EGFR基因突变情况。
结果肺腺癌组织中PTEN蛋白的表达显著低于正常肺组织，EMMPRIN蛋白的表达显著高于正常肺组织。PTEN和EMMPRIN表达率为40%（36/90）和80%（72/90），EGFR基因突变率为47.78%（43/90）。PTEN的表达与肺腺癌组织学类型有关（P=0.000），EMMPRIN的表达与淋巴结转移状况及TNM分期有关（均P < 0.05）。Spearman相关分析显示PTEN和EMMPRIN呈显著负相关（rp=-0.215, P=0.041）, PTEN与EGFR基因突变呈正相关（rp=0.490, P=0.000），EMMPRIN与EGFR基因突变无明显相关性（rp=0.170, P=0.110）。
结论肺腺癌中PTEN和EMMPRIN蛋白可能存在某些机制共同作用促进了肺腺癌的发生发展，PTEN蛋白的表达与EGFR基因突变呈正相关。
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关键词:
- 肺腺癌 /
- PTEN /
- EMMPRIN/CD147 /
- EGFR基因突变
Abstract:ObjectiveTo investigate the expression of PTEN and EMMPRIN and their relationships with clinicopathological factors and EGFR mutation in lung adenocarcinoma tissues.
MethodsThe expression of PTEN and EMMPRIN proteins were examined in 90 cases of lung adenocarcinoma tissues by immunohistochemical method, and 10 cases of normal lung tissues were taken as control. The mutation of EGFR was detected using PCR.
ResultsPTEN expression in lung adenocarcinoma tissues was significantly lower than that in non-neoplastic internal controls tissues. EMMPRIN expression in lung adenocarcinoma tissues was significantly higher than that in internal controls tissues. The positive rates of PTEN and EMMPRIN expression were 40%(36/90) and 80%(72/90), respectively. EGFR gene mutation rate was 47.78%(43/90). The expression of PTEN was positively correlated with the histological subtypes (P=0.000). EMMPRIN expression was positively correlated with lymph node metastasis status and TNM stage (both P=0.000). Spearman correlation analysis showed that PTEN expression was negatively correlated with EMMPRIN expression (rp=-0.215, P=0.041). PTEN expression had a positive correlation with EGFR mutation (rp=0.490, P=0.000). EMMPRIN expression had no correlation with EGFR mutation (rp=0.170, P=0.110).
ConclusionPTEN and EMMPRIN may have a synergistic effect on the progression and development of lung adenocarcinoma. PTEN expression has a positive correlation with EGFR mutation which may provide evidences for targeted therapy.
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Key words:
- Lung adenocarcinoma /
- PTEN /
- EMMPRIN/CD147 /
- EGFR mutation
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图 1 PTEN和CD147在肺腺癌组织中的表达（IHC×200）
Figure 1 Expression of PTEN and CD147 in lung adenocarcinoma tissues (IHC×200)
表 1 PTEN和CD147的表达与肺腺癌患者临床病理特征的关系
Table 1 Relationship between expression of PTEN and CD147 with clinicopathological characteristics of lung adenocarcinoma patients
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表 2 肺腺癌组织中PTEN和CD147表达的相关分析 (n)
Table 2 Spearman analysis of PTEN and CD147 expression in lung adenocarcinoma tissues (n)
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表 3 PTEN和CD147与肺腺癌患者EGFR基因突变的关系 (n)
Table 3 Spearman analysis of PTEN and CD147 expression with EGFR mutation in lung adenocarcinoma patients (n)
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[1] Xu XY, Lin N, Li YM, et al.Expression of HAb18G/CD147 and its localization correlate with the progression and poor prognosis of non-small cell lung cancer[J].Pathol Res Pract, 2013, 209(6): 345-52. doi: 10.1016/j.prp.2013.02.015
[2] Tay Y, Kats L, Salmena L, et al.Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs[J].Cell, 2011, 147(2): 344-57. doi: 10.1016/j.cell.2011.09.029
[3] Chen Y, van de Vijver MJ, Hibshoosh H, et al.PTEN and NEDD4 in Human Breast Carcinoma[J].Pathol Oncol Res, 2016, 22(1): 41-7. doi: 10.1007/s12253-015-9971-2
[4] Shen H, Guan D, Shen J, et al.TGF-β1 induces erlotinib resistance in non-small cell lung cancer by down-regulating PTEN[J].Biomed Pharmacother, 2016, 77: 1-6. doi: 10.1016/j.biopha.2015.10.018
[5] Lotan TL, Wei W, Morais CL, et al.PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer[J].Eur Urol Focus, 2016, 2(2): 180-8. doi: 10.1016/j.euf.2015.07.005
[6] 梁育飞, 郑国启, 李春英, 等.COX-2、NF-κB、WT-1、PTEN在恶性腹膜间皮瘤中的表达及与预后的关系[J].肿瘤防治研究, 2016, 43(8):704-8. doi: 10.3971/j.issn.1000-8578.2016.08.011 Liang YF, Zheng GQ, Li CY, et al.Prognostic Significance of COX-2, NF-κB, WT-1 and PTEN Expression in Malignant Peritoneal Mesothelioma[J].Zhong Liu Fang Zhi Yan Jiu, 2016, 43(8): 704-8. doi: 10.3971/j.issn.1000-8578.2016.08.011
[7] Lee A, Rode A, Nicoll A, et al.Circulating CD147 predicts mortality in advanced hepatocellular carcinoma[J].J Gastroenterol Hepatol, 2016, 31(2): 459-66. doi: 10.1111/jgh.2016.31.issue-2
[8] Kaira K, Arakawa K, Shimizu K, et al.Relationship between CD147 and expression of amino acid transporters (LAT1 and ASCT2) in patients with pancreatic cancer[J].Am J Transl Res, 2015, 7(2): 356-63. http://www.ajtr.org/files/ajtr0003635.pdf
[9] 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[J].Mol Cell Biochem, 2013, 383(1-2): 1-11. doi: 10.1007/s11010-013-1722-7
[10] 许建民, 董涛, 田湘萍, 等.PTEN和AKT2及CD147在胃癌组织中的表达及意义[J].中国现代普通外科进展, 2010, 13(9): 681-4. http://www.cnki.com.cn/Article/CJFDTOTAL-PWJZ201009006.htm Xu JM, Dong T, Tian XP, et al.Expression of PTEN and CD147 and AKT2 in gastric carcinoma tissues and the clinical significance[J].Zhongguo Xian Dai Pu Tong Wai Ke Jin Zhan, 2010, 13(9): 681-4. http://www.cnki.com.cn/Article/CJFDTOTAL-PWJZ201009006.htm
[11] 李昌秀, 徐红梅, 杨达荣, 等.CD147PTEN E-钙黏蛋白在食管癌组织中表达与临床病理的关系[J].检验医学与临床, 2013, 10(2): 129-31. http://www.cnki.com.cn/Article/CJFDTOTAL-JYYL201302002.htm Li CX, Xu HM, Yang DR, et al.The expression of CDl47, PTEN and E-cadherin in esophagcal carcinoma and their correlation with clinical-pathological characteristics[J].Jian Yan Yi Xue Yu Lin Chuang, 2013, 10(2): 129-31. http://www.cnki.com.cn/Article/CJFDTOTAL-JYYL201302002.htm
[12] 徐小艳, 郅程, 陈清, 等.非小细胞肺癌组织中PTEN和HAb18G的表达及相关关系研究[J].实用医学杂志, 2012, 28(5): 701-4. http://www.cnki.com.cn/Article/CJFDTOTAL-SYYZ201205008.htm Xu XY, Zhi C, Chen Q, et al.Study on the correlation of PTEN and HAb18G expression in non small lung carcinoma tissues[J].Shi Yong Yi Xue Za Zhi, 2012, 28(5): 701-4. http://www.cnki.com.cn/Article/CJFDTOTAL-SYYZ201205008.htm
[13] 刘曙光, 邹振宁, 马红梅, 等.CD147和PTEN在非小细胞肺癌中的表达及与临床病理因素的相关性分析[J].重庆医学, 2016, 45(19): 2638-40, 2644. doi: 10.3969/j.issn.1671-8348.2016.19.015 Liu SG, Zou ZN, Ma HM, et al.The expression of CD147 and PTEN in non small cell lung cancer and their correlation with clinical pathological factors[J].Chongqing Yi Xue, 2016, 45(19): 2638-40, 2644. doi: 10.3969/j.issn.1671-8348.2016.19.015
[14] 顾学文, 陈月香, 田秀春, 等.PTEN抑癌基因在人胃癌组织中的表达及意义[J].肿瘤研究与临床, 2005, 17(1): 18-20. http://www.cnki.com.cn/Article/CJFDTOTAL-ZLYJ200501007.htm Gu XW, Chen YX, Tian XC, et al.Expression and significance of suppressor gene PTEN in human gastric cancer tissues[J].Zhong Liu Yan Jiu Yu Lin Chuang, 2005, 17(1): 18-20. http://www.cnki.com.cn/Article/CJFDTOTAL-ZLYJ200501007.htm
[15] 米登海, 易继林, 刘恩宇, 等.血管内皮生长因子与抑癌基因PTEN在肝细胞癌组织中表达及临床意义[J].中华肿瘤防治杂志, 2006, 13(15): 1158-62. doi: 10.3969/j.issn.1673-5269.2006.15.010 Mi DH, Yi JL, Liu EY, et al.Expressions of VEGF and PTEN in liver cancer and their clinical significance[J].Zhonghua Zhong Liu Fang Zhi Za Zhi, 2006, 13(15): 1158-62. doi: 10.3969/j.issn.1673-5269.2006.15.010
[16] Moon SK, Kim HM, Kim CH.PTEN induces G1, cell cycle arrest and inhibits MMP-9 expression via the regulation of NF-κB and AP-1 in vascular smooth muscle cells[J].Arch Biochem Biophys, 2004, 421(2): 267-76. doi: 10.1016/j.abb.2003.11.007
[17] Tian T, Nan KJ, Wang SH, et al.PTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and-independent mechanisms in HepG2 cells[J].Carcinogenesis, 2010, 31(7): 1211-9. doi: 10.1093/carcin/bgq085
[18] Marchiq I, Albrengues J, Granja S, et al.Knock out of the BASIGIN/CD147 chaperone of lactate/H+symporters disproves its pro-tumour actionviaextracellular matrix metalloproteases (MMPs) induction[J].Oncotarget, 2015, 6(28): 24636-48. doi: 10.18632/oncotarget
[19] Su J, Chen X, Kanekura T.A CD147-targeting siRNA inhibits the proliferation, invasiveness, and VEGF production of human malignant melanoma cells by down-regulating glycolysis[J].Cancer Lett, 2009, 273(1): 140-7. doi: 10.1016/j.canlet.2008.07.034
[20] 贺锐, 李建民, 王跃华, 等.EGFR基因突变与肺腺癌新分类及临床病理特征的关系[J].临床与实验病理学杂志, 2013, 29(12): 1323-8. http://cdmd.cnki.com.cn/Article/CDMD-10114-1014318506.htm He R, Li JM, Wang YH, et al.Correlation of epidermal growth factor receptor mutations with the new lung adenocarcinoma classification and their clinicopathological features[J].Lin Chuang Yu Shi Yan Bing Li Xue Za Zhi, 2013, 29(12): 1323-8. http://cdmd.cnki.com.cn/Article/CDMD-10114-1014318506.htm
[21] Hong SJ, Kim TJ, Choi YW, et al.Radiogenomic correlation in lung adenocarcinoma with epidermal growth factor receptor mutations: Imaging features and histological subtypes[J].Eur Radiol, 2016, 26(10): 3660-8. doi: 10.1007/s00330-015-4196-z
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