舌鳞状细胞癌中EphA7的表达及其与患者病理参数和预后的相关分析

上海口腔医学 ›› 2014, Vol. 23 ›› Issue (5): 575-579.

舌鳞状细胞癌中EphA7的表达及其与患者病理参数和预后的相关分析

李丹¹, 向彬², 英晓霞³, 董会⁴

1.大连医科大学附属第二医院肿瘤科,辽宁大连 116027; 2.大连大学口腔医学院,辽宁大连 116622; 3.大连医科大学口腔医学院,辽宁大连 116044; 4.大连医科大学附属第一医院口腔科,辽宁大连 116011

收稿日期:2014-07-18 修回日期:2014-08-28 出版日期:2014-10-20 发布日期:2015-02-04
通讯作者: 董会,E-mail：donghui760413@sina.com
作者简介:李丹（1979-）,女,博士,主治医师,E-mail:donghui760413@sina.com
基金资助:
国家自然科学基金（81371161）

Correlation analysis of EphA7 expression with clinico-pathological parameters and prognosis in tongue squamous cell carcinoma

LI Dan¹, XIANG Bing², YING Xiao-xia³, DONG Hui⁴

1.Department of Oncology, the Second Affiliated Hospital of Dalian Medical University. Dalian 116027; 2.College of Stomatology, Dalian University. Dalian 116622; 3. College of Stomatology, Dalian Medical University. Dalian 116044; 4. Department of Stomatology, the First Affiliated Hospital of Dalian Medical University. Dalian 116011, Liaoning Province, China

Received:2014-07-18 Revised:2014-08-28 Online:2014-10-20 Published:2015-02-04
Supported by:
; Supported by National Natural Science Foundation of China (81371161)

摘要/Abstract

摘要： 目的检测舌鳞状细胞癌（tongue squamous cell carcinoma, TSCC）中EphA7的表达,分析其表达水平与TSCC患者临床病理参数及预后的相关性。方法应用免疫组织化学方法检测54例TSCC及配对癌旁正常组织中EphA7的表达水平,结合随访数据,分析EphA7表达水平与肿瘤病理参数、总体及无瘤生存期的关系。下调SCC9细胞系EphA7的表达水平,检测肿瘤细胞的侵袭、转移能力。采用SPSS17.0软件包进行配对资料t检验和生存分析。结果所有TSCC组织中均发现EphA7阳性表达,EphA7高表达与不伴淋巴结转移（P<0.05）、无血管浸润（P<0.05）、致密基质细胞炎症反应（P<0.01）以及女性（P<0.05）密切相关;与EphA7低表达患者相比,EphA7高表达组表现出更长的总生存期及无瘤生存期（P<0.05）。下调EphA7表达的SCC9细胞侵袭、转移能力显著增高（P<0.05）。结论 EphA7参与肿瘤恶性进程,影响患者预后,有可能作为TSCC潜在的治疗靶点。

关键词: 舌鳞状细胞癌, EphA7, SCC9

Abstract: PURPOSE: To evaluate the relationship between the expression of EphA7 and its clinical correlation and function with tongue squamous cell carcinoma (TSCC). METHODS: The expression of EphA7 was determined in 54 pairs of human TSCC tissues and pair-matched adjacent noncancerous tissues by immunohistochemistry. Furthermore, association between EphA7 expression and patients’ clinicopathological characteristics, overall and disease-free survival were evaluated. Invasion and metastasis of SCC9 cell were detected before and after down regulation of EphA7 expression. Differences in measurement data were compared with paired-t test, and survival analysis was made by Kaplan-Meier method using SPSS17.0 software package. RESULTS: EphA7 was positive in all examined specimens. Significant associations were noted between high EphA7 expression and absence of lymph node metastasis, absence of vascular invasion, dense stromal inflammatory reaction and female gender. TSCC patients with higher EphA7 expression presented longer overall and disease-free survival compared with low EphA7 expression. The invasion and metastasis of SCC9 cell increased significantly after down regulation of EphA7. CONCLUSIONS: The study indicated that EphA7 may participate in the malignant transformation of TSCC, reinforcing their utility as targets for potential therapeutic intervention.

Key words: TSCC, EphA7, SCC9

李丹, 向彬, 英晓霞, 董会. 舌鳞状细胞癌中EphA7的表达及其与患者病理参数和预后的相关分析[J]. 上海口腔医学, 2014, 23(5): 575-579.

LI Dan, XIANG Bing, YING Xiao-xia, DONG Hui. Correlation analysis of EphA7 expression with clinico-pathological parameters and prognosis in tongue squamous cell carcinoma[J]. Shanghai Journal of Stomatology, 2014, 23(5): 575-579.

参考文献

[1] Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease [J]. Cell, 2008, 133(1): 38-52.
[2] Brandley-Sieders DM, Chen J. Eph receptor tyrosine kinase in angiogenesis: from development to disease[J]. Angiogenesis, 2004, 7(1): 17-28.
[3] Castaño J, Davalos V, Schwartz S Jr, et al. EPH receptors in cancer [J]. Histol Histopathol, 2008, 23(8): 1011-1023.
[4] Jemal A, Siegel R,Ward E, et al. Cancer statistics, 2007[J]. CA Cancer J Clin, 2007, 57(1): 43-66.
[5] Sano D, Myers JN. Metastasis of squamous cell carcinoma of the oral tongue [J]. Cancer Metastasis Rev, 2007, 26(3-4): 645-662.
[6] Wu J, Luo H. Recent advances on T-cell regulation by receptor tyrosine kinases [J]. Curr Opin Hematol, 2005, 12(4): 292-297.
[7] Nakanishi H, Nakamura T, Canaani E, et al. ALL1 fusion proteins induce deregulation of EphA7 and ERK phosphorylation in human acute leukemia [J]. Proc Natl Acad Sci USA, 2007, 104(36): 14442-14427.
[8] López-Nieva P, Vaquero C, Fern&#x0dbc0;&#x0dda6;ndez-Navarro P, et al. EPHA7, a new target gene for 6q deletion in T-cell lymphoblastic lymphomas [J]. Carcinogenesis, 2012, 33(2): 452-458.
[9] Brantley-Sieders DM, Jiang A, Sarma K, et al. Eph/ephrin profiling in human breast cancer reveals significant associations between expression level and clinical outcome [J]. PLoS One, 2011, 6(9): e24426.
[10] Wang J, Kataoka H, Suzuki M, et al. Downregulation of EphA7 by hypermethylation in colorectal cancer[J]. Oncogene,2005,24(36): 5637-5647.
[11] Oudes AJ, Roach JC, Walashek LS, et al. Application of Affymetrix array and Massively Parallel Signature Sequencing for identification of genes involved in prostate cancer progression [J]. BMC Cancer, 2005, 5: 86.
[12] Wang J, Li G, Ma H, et al. Differential expression of EphA7 receptor tyrosine kinase in gastric carcinoma[J]. Hum Pathol, 2007, 38(11): 1649-1656.
[13] Giaginis C, Tsoukalas N, Bournakis E, et al. Ephrin (Eph) receptor A1, A4, A5 and A7 expression in human non-small cell lung carcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients’ survival [J]. BMC Clin Pathol, 2014, 14(1): 8.