Expressions of claudin-3， claudin-7 in nasopharyngeal carcinoma
CHEN Ru1 SU Xiaoqing1 PAN Shenghua2 CHEN Liaozhi1 ZHOU Jing1 HUANG Yideng3▲
1.Department of Otolaryngology, the Third Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou 325200, China;
2.Department of Pathology, the Third Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou 325200, China;
3.Department of ENT & HN Surgery, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou 325000, China
Abstract：Objective To explore the expression of claudin-3, claudin-7 in patients with nasopharyngeal carcinoma(NPC) and to analyze the relationship between the proteins and clinical significance. Methods Fifty-two archival paraffin embedded tissue specimens of nasopharyngeal were retrospectively analyzed from January 2014 to January 2016 at the Third Affiliated Hospital of Wenzhou Medical University. Another 20 samples of Histologically normal nasopharyngeal tissues were also obtained as control group. Immunohistochemstry was used to detect the expression of claudin-3 and claudin-7 in the different tissues, and the relationship was analyzed between the expression and clinic pathological parameter. The relationship of the expression levels of claudin-3 and claudin-7 in nasopharyngeal carcinoma tissues was analyzed. Results There was no statistically significant difference in the positive expression rate of claudin-3 (51.92%) between nasopharyngeal carcinoma and adjacent non-neoplastic tissues (45.00%) (P ＞ 0.05). While the positive expression rate of claudin-7 in nasopharyngeal carcinomas (26.92%), in comparison with the adjacent non-neoplastic tissues (55.00%), there was significant difference (P = 0.025). The positive expression rate of claudin-3 in the Ⅲ+Ⅳ stage patients was significantly higher than that in the Ⅰ+Ⅱ stage patients (P = 0.002). Compared with the positive expression rate of claudin-7 in nasopharyngeal carcinomas without cervical lymph node metastasis (9/15), the positive expression rate in nasopharyngeal carcinomas with cervical lymph node metastasis was remarkably lower (5/37) (P = 0.001). Correlation analysis results showed that there was no relationship between expression of claudin-3 and claudin-7 (r = 0.2696, P = 0.0532). Conclusion claudin-3 relates to the TNM tumor staging, in consideration of the effect in the nasopharyngeal carcinoma progress. claudin-7 decreased expression plays a role in the occurrence and development of nasopharyngeal carcinoma. claudin-3 and claudin-7 may be novel biomarkers for the new target for nasopharyngeal carcinoma treatment.
[1] Khan N，Asif R. Transcriptional regulators of claudins in epithelial tight junctions [J]. Mediators Inflamm，2015：219 843．
[2] Cohen EE，Lingen MW，Vokes EE. The expanding role of systemic therapy in head and neck cancer [J]. J Clin Oncol，2004，22（9）：1743-1752.
[3] Wong AS，Soo RA，Lu JJ，et al. Paclitaxel，5-fluorouracil and hydroxyurea concurrent with radiation in locally advanced nasopharyngeal carcinoma [J]. Ann Oncol，2006， 17（7）：1152-1157.
[4] Sun X，Su S，Chen C，et al. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma：an analysis of survival and treatment toxicities [J]. Radiother Oncol，2014，110（3）：398-403.
[5] Li X，Liu X，Li CY，et al. Recombinant adeno-associated virus mediated RNA interference inhibits metastasis of nasopharyngeal cancer cells in vivo and in vitro by suppression of Epstein-Barr virus encoded LMP-1 [J]. Int J Oncol，2006，29（3）：595-603.
[6] Zhang M，Zhang Z，Pan HY，et al. TGF-betal induces human bronchial epithelial cell-to-mesenchymal transition in vitro [J]. Lung，2009，187（3）：187-194.
[7] Zihni C，Mills C，Matter K，et al. Tight junctions：From simple barriers to multifunctional molecular gates [J]. Nat Rev Mol Cell Biol，2016，17（9）：564-580.
[8] Singh AB，Sharma A，Dhawan P. Claudin family of proteins and cancer：an overview [J]. J oncol，2010：1-11.
[9] Soini Y. Expression of claudinsl，2，3，4，5 and 7 in various types of tumors [J]. Histopathology，2005，46：551-560.
[10] Kominsky SL，Vali M，Korz D，et al. Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins claudin 3 and 4 [J] Am J Pathol，2004，164（5）：1627-1633.
[11] 李婧宜，谢芳，徐晓平，等.Claudin-3在结直肠癌中的表达及意义[J].J South Med Univ，2017，37（1）：63-67.
[12] 鄢少聪，应学明.紧密连接相关蛋白在肺癌脑转移瘤中的表达及临床意义[J].癌症进展，2018，16（4）：475-479.
[13] Yamauchi K，Rai T，Kobayashi K，et al. Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins [J]. Proc Natl Acad Sci USA，2004，101（13）：4690-4694.
[14] 吴引萍，郭树林.冰片对血脑肿瘤屏障开放程度及紧密连接蛋白表达的影响[J].癌症进展，2016，14（10）：986-988，992.
[15] Shang X，Lin X，Alvarez E，et al. Tight junction proteins claudin-3 and claudin-4 control tumor growth and metastases [J]. Neoplasia，2012，14（10）：974-985.
[16] Sun P，Chen C，Chen XL，et al. Proposal of a clinical typing system and generation of a prognostic model in patients with nasopharyngeal carcinoma from Southern China [J]. J BUON，2014，19（2）：474-483.
[17] 邹浩元，黄国栋，郑坚，等.EB病毒VCA-IgA抗体与鼻咽癌预后的关系[J].陕西肿瘤医学，2001，9（1）：6-7.
[18] Al Moustafa AE，Alaoui-Jamali MA，BatiSt G，et al. Identification of genes associated with head and neck carcinogenesis by eDNA micronrray comparison between matched primary normal epithelial and squamous carcinoma cells [J]. Oncogene，2002，21（17）：2634-2640.
[19] Suren D，Yildirim M，Kaya V，et al. Expression patterns of claudins 1，4，and 7 and their prognostic significance in nasopharyngeal carcinoma [J]. Jbuon，2015，20（1）：212-217.
[20] Kondoh A，Takano K，Kojima T，et al. Altered expression of claudin-1，claudin-7，and tricellulin regardless of human papilloma virus infection in human tonsillar squamous cell carcinoma [J]. Acta Otolaryngol，2011，131（8）：861-868.
[21] Kapral M，Strzalka-Mrozik B，Kowalczyk M，et al. Transcriptional activities of histone H3，cyclin D1 and claudin7 encoding genes in laryngeal cancer [J]. Eur Arch Otorhinolaryngol，2011，268（5）：709-714.
[22] 王昆，王晓楠，丁磊.抑癌基因Claudin-7的研究进展[J].医学综述，2018，24（4）：625-630.
[23] Ikenouchi J，Matsuda M，Furuse M，et al. Regulation of tight junctions during the epithelium-mesenchyme transition：direct repression of the gene expression of claudins／occludin by snail [J]. J Cell Sci，2003，116（pt 10）：1959-1967.
[24] Nakayama F，Semba S，Usami Y，et a1. Hypermethlation-modulated down regulation of claudin-7 promotes the progression of colorectal carcinoma [J]. Pathobiology，2008， 75（3）：177-185.
[25] Taharies S，Siegel PM. The role of claudins in cancer metastasis [J]. Oncogene，2017，36（9）：1170-1190.
[26] Chuen H，Yu-Sun C，Ngan-Ming T，et al. Expression pattern and prognostic significance of claudins 1，4，and7 in nasopharyngeal carcinoma [J]. Hum Pathol，2010，41（7）：944-950.
2018, Vol. 15 
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