Claudin-4 Expression Predicts Survival in Pancreatic Ductal Adenocarcinoma
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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.
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.
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).
Increased expression of CLDN4 mRNA predicts better prognosis in PDAC.
KeywordsChronic Pancreatitis Pancreatic Ductal Adenocarcinoma Pancreatic Cancer Cell Line FFPE Sample Normal Pancreatic Tissue
Supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Conflict of interest
The authors declare no conflict of interest.
- 13.Yamamoto H, Itoh F, Iku S, Adachi Y, Fukushima H, Sasaki S, et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol. 2001;19:1118–27.PubMedGoogle Scholar
- 14.Jones LE, Humphreys MJ, Campbell F, Neoptolemos JP, Boyd MT. Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: increased expression of matrix metalloproteinase-7 predicts poor survival. Clin Cancer Res. 2004;10:2832–45.PubMedCrossRefGoogle Scholar
- 17.Niedergethmann M, Hildenbrand R, Wostbrock B, Hartel M, Sturm JW, Richter A, et al. High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas. Pancreas. 2002;25:122–9.PubMedCrossRefGoogle Scholar
- 31.Hruban RH, Boffetta P, Hiraoka N, et al. Ductal adenocarcinoma of the pancreas. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. Lyon, France: IARC Press; 2010. p. 281–91.Google Scholar
- 32.Sobin L, Wittekind C. Union Internationale Contre le Cancer and the American Joint Committee on Cancer. In: TNM Classification of Malignant Tumors. 6th ed. New York: Wiley-Liss; 2002.Google Scholar
- 33.Ohuchida K, Mizumoto K, Ogura Y, Ishikawa N, Nagai E, Yamaguchi K, et al. Quantitative assessment of telomerase activity and human telomerase reverse transcriptase messenger RNA levels in pancreatic juice samples for the diagnosis of pancreatic cancer. Clin Cancer Res. 2005;11:2285–92.PubMedCrossRefGoogle Scholar
- 34.Abrahamsen HN, Steiniche T, Nexo E, Hamilton-Dutoit SJ, Sorensen BS. Towards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction: a methodological study on lymph nodes from melanoma patients. J Mol Diagn. 2003;5:34–41.PubMedCrossRefGoogle Scholar