Expression and Significance of Claudin-1 in Non-small Cell Lung Cancer_West China Medical Journal

Authors：

CHEN Shigao ^1,2 , WANG Shifeng ¹ , GAO Jun ¹ ,  ZHANG Shangfu ¹

1. Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China; 2. Department of Pathology, Gaoxin Daan Clinical Laboratory, Chengdu, Sichuan 611731, P. R. China;

Corresponding?author：

ZHANG Shangfu, Email: lululucsg@tom.com

Keywords：

Claudin-1; 非小細胞肺癌; 組織芯片; 預后

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目的　檢測Claudin-1蛋白在非小細胞肺癌（NSCLC）原發癌組織及其淋巴結轉移癌組織中的表達，并探討其與NSCLC各臨床病理特征和預后的關系。方法　利用組織芯片技術，采用免疫組織化學染色方法檢測Claudin-1在1998年1月－2003年12月收集的279例NSCLC原發癌組織及其55例淋巴結轉移癌組織、54例癌旁正常肺組織中的表達。運用SPSS 13.00統計軟件對相關數據進行統計分析。結果　Claudin-1在279例NSCLC原發癌組織和55例淋巴結轉移癌組織中的陽性表達率分別為69.9%和50.9%，在鱗癌和腺癌中的陽性表達率分別為83.7%和55.7%，在高、中分化癌組和低分化癌組中的陽性表達率分別為78.6%和62.7%。Claudin-1在原發癌組織中的陽性表達率高于其淋巴結轉移癌組織（P＜0.05）；在鱗癌中的陽性表達率高于腺癌（P＜0.05），且在高、中分化癌組中的陽性表達率高于低分化癌（P＜0.05）。Claudin-1陽性表達之NSCLC患者的生存率高于陰性表達者（P＜0.05）。結論　Claudin-1在NSCLC中的表達與患者的組織學類型及病理分級有關，且Claudin-1是NSCLC侵襲、轉移的抑制因子，并且可能是一個有用的預后因子。

Citation： CHEN Shigao,WANG Shifeng,GAO Jun,ZHANG Shangfu. Expression and Significance of Claudin-1 in Non-small Cell Lung Cancer. West China Medical Journal, 2012, 27(7): 1036-1039. doi: Copy

1.	Heiskala M, Peterson PA, Yang Y. The roles of claudin superfamily proteins in paracellular transport[J]. Traffic, 2001, 2(2): 93-98.
2.	Li Z, Huang C, Bai S, et al. Prognostic evaluation of epidermal fatty acid-binding protein and calcyphosine, two proteins implicated in endometrial cancer using a proteomic approach[J]. Int J Cancer, 2008, 123(10): 2377-2383.
3.	Swisshelm K, Macek R, Kubbies M. Role of claudins in tumorigenesis[J]. Adv Drug Deliv Rev, 2005, 57(6): 919-928.
4.	Lee JW, Lee SJ, Seo J, et al. Increased expressions of claudin-1 and claudin-7 during the progression of cervical neoplasia[J]. Gynecol Oncol, 2005, 97(1): 53-59.
5.	Yoon CH, Kim MJ, Park MJ, et al. Claudin-1 acts through c-Abl-protein kinase Cdelta (PKCdelta) signaling and has a causal role in the acquisition of invasive capacity in human liver cells[J]. J Biol Chem, 2010, 285(1): 226-233.
6.	Dhawan P, Singh AB, Deane NG, et al. Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer[J]. J Clin Invest, 2005, 115(7): 1765-1776.
7.	Dos Reis PP, Bharadwaj RR, Machado J, et al. Claudin 1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma[J]. Cancer, 2008, 113(11): 3169-3180.
8.	Chao YC, Pan SH, Yang SC, et al. Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma[J]. Am J Respir Crit Care Med, 2009, 179(2): 123-133.
9.	Miwa N, Furuse M, Tsukita S, et al. Involvement of claudin-1 in the β-catenin/TCF signaling pathway and its frequent upregulation in human colorectal cancers[J]. Oncol Res, 2001, 12(11-12): 469-476.
10.	Hoevel T, Macek R, Swisshelm K, et al. Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids[J]. Int J Cancer, 2004, 108(3): 374-383.
11.	Chang TL, Ito K, Ko TK, et al. Claudin-1 has tumor suppressive activity and is a direct target of RUNX3 in gastric epithelial cells[J]. Gastroenterology, 2010, 138(1): 255-265.
12.	Jung JH, Jung CK, Choi HJ, et al. Diagnostic utility of expression of claudins in non-small cell lung cancer: different expression profiles in squamous cell carcinomas and adenocarcinomas[J]. Pathol Res Pract, 2009, 205(6): 409-416.
13.	Paschoud S, Bongiovanni M, Pache JC, et al. Claudin-1 and claudin-5 expression patterns differentiate lung squamous cell carcinomas from adenocarcinomas[J]. Mod Pathol, 2007, 20(9): 947-954.
14.	Moldvay J, Jackel M, Paska C, et al. Distinct claudin expression profile in histologic subtypes of lung cancer[J]. Lung Cancer, 2007, 57(2): 159-167.
15.	Merikallio H, Kaarteenaho R, Pääkkö P, et al. Impact of smoking on the expression claudins in lung carcinoma[J]. Eur J Cancer, 2011, 47(4): 620-630.

1. 　Heiskala M, Peterson PA, Yang Y. The roles of claudin superfamily proteins in paracellular transport[J]. Traffic, 2001, 2(2): 93-98.
2. 　Li Z, Huang C, Bai S, et al. Prognostic evaluation of epidermal fatty acid-binding protein and calcyphosine, two proteins implicated in endometrial cancer using a proteomic approach[J]. Int J Cancer, 2008, 123(10): 2377-2383.
3. 　Swisshelm K, Macek R, Kubbies M. Role of claudins in tumorigenesis[J]. Adv Drug Deliv Rev, 2005, 57(6): 919-928.
4. 　Lee JW, Lee SJ, Seo J, et al. Increased expressions of claudin-1 and claudin-7 during the progression of cervical neoplasia[J]. Gynecol Oncol, 2005, 97(1): 53-59.
5. 　Yoon CH, Kim MJ, Park MJ, et al. Claudin-1 acts through c-Abl-protein kinase Cdelta (PKCdelta) signaling and has a causal role in the acquisition of invasive capacity in human liver cells[J]. J Biol Chem, 2010, 285(1): 226-233.
6. 　Dhawan P, Singh AB, Deane NG, et al. Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer[J]. J Clin Invest, 2005, 115(7): 1765-1776.
7. 　Dos Reis PP, Bharadwaj RR, Machado J, et al. Claudin 1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma[J]. Cancer, 2008, 113(11): 3169-3180.
8. 　Chao YC, Pan SH, Yang SC, et al. Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma[J]. Am J Respir Crit Care Med, 2009, 179(2): 123-133.
9. 　Miwa N, Furuse M, Tsukita S, et al. Involvement of claudin-1 in the β-catenin/TCF signaling pathway and its frequent upregulation in human colorectal cancers[J]. Oncol Res, 2001, 12(11-12): 469-476.
10. 　Hoevel T, Macek R, Swisshelm K, et al. Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids[J]. Int J Cancer, 2004, 108(3): 374-383.
11. 　Chang TL, Ito K, Ko TK, et al. Claudin-1 has tumor suppressive activity and is a direct target of RUNX3 in gastric epithelial cells[J]. Gastroenterology, 2010, 138(1): 255-265.
12. 　Jung JH, Jung CK, Choi HJ, et al. Diagnostic utility of expression of claudins in non-small cell lung cancer: different expression profiles in squamous cell carcinomas and adenocarcinomas[J]. Pathol Res Pract, 2009, 205(6): 409-416.
13. 　Paschoud S, Bongiovanni M, Pache JC, et al. Claudin-1 and claudin-5 expression patterns differentiate lung squamous cell carcinomas from adenocarcinomas[J]. Mod Pathol, 2007, 20(9): 947-954.
14. 　Moldvay J, Jackel M, Paska C, et al. Distinct claudin expression profile in histologic subtypes of lung cancer[J]. Lung Cancer, 2007, 57(2): 159-167.
15. 　Merikallio H, Kaarteenaho R, Pääkkö P, et al. Impact of smoking on the expression claudins in lung carcinoma[J]. Eur J Cancer, 2011, 47(4): 620-630.

West China Medical Journal

Expression and Significance of Claudin-1 in Non-small Cell Lung Cancer

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