Claudin-4 Expression Predicts Survival in Pancreatic Ductal Adenocarcinoma
Claudin-4 Expression Predicts Survival in Pancreatic Ductal Adenocarcinoma
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DOI：
10.1245/s10434-011-1970-2
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发表时间：
2012-07-01
影响因子：
3.7
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
--
作者：
Tsutsumi, Kosuke;Sato, Norihiro;Tanaka, Masao
背景资料。胰腺导管腺癌(PDAC)患者预后标志物的识别有助于临床治疗。Claudin-4(CLDN4)最近被发现在PDAC中高表达，其临床相关性尚不清楚。方法：研究方法。应用实时定量逆转录聚合酶链式反应(qRT-PCR)技术，检测了100例PDAC患者9个胰腺癌细胞系和福尔马林固定石蜡包埋(FFPE)组织中CLDN4mRNA的表达。然后，CLDN4的表达水平与临床病理变量和患者预后相关。应用免疫组织化学方法检测20例PDAC FFPE组织中CLDN4蛋白的表达。结果。与正常导管上皮细胞和成纤维细胞相比，所有受试胰腺癌细胞系中CLDN4的表达均增强。我们发现低表达CLDN4与PDAC患者较短的生存期显著相关(风险比：1.362，95%可信区间；1.011-1.873，P=0.0419)。CLDN4高表达患者的中位生存期为63.0月，低于CLDN4低表达患者的14.7月(P=0.0067)。免疫组织化学分析显示，CLDN4mRNA表达水平与CLDN4蛋白表达呈显著正相关(P=0.0168)。结论。CLDN4基因的高表达预示着PDAC预后较好。
Background. Identification of prognostic markers would be useful in the clinical management of patients with pancreatic ductal adenocarcinoma (PDAC). The clinical relevance of claudin-4 (CLDN4), recently identified as overexpressed in PDAC, is unknown. Methods. Using quantitative real-time reverse transcription- polymerase chain reaction (qRT-PCR), we analyzed CLDN4 mRNA expression in a panel of 9 pancreatic cancer cell lines and formalin-fixed paraffin-embedded (FFPE) tissues from 100 patients with PDAC. The CLDN4 expression levels were then correlated with clinicopathological variables and patient outcome. We also performed immunohistochemical analysis in 20 FFPE samples of PDAC to investigate the expression of CLDN4 protein. Results. Increased expression of CLDN4 was confirmed in all the pancreatic cancer cell lines tested compared with normal ductal epithelial cells and fibroblasts. We found that low expression of CLDN4 was significantly associated with shorter survival in patients with PDAC (hazard ratio; 1.362, 95% confidence interval; 1.011-1.873, P = 0.0419). Patients with high CLDN4 expression survived longer for a median of 63.0 months, compared with 14.7 months in patients with low CLDN4 expression (P = 0.0067). In immunohistochemical analysis, the level of CLDN4 mRNA expression was significantly correlated with the expression of CLDN4 protein (P = 0.0168). Conclusion. Increased expression of CLDN4 mRNA predicts better prognosis in PDAC.