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Expression of claudin 1, claudin 4, and claudin 7 in colorectal cancer and its relation with CLDN DNA methylation patterns
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Orebro Univ, Fac Med & Hlth, Dept Clin Res, Orebro, Sweden..
Orebro Univ, Fac Med & Hlth, Dept Clin Res, Orebro, Sweden..
Orebro Univ, Fac Med & Hlth, Dept Clin Res, Orebro, Sweden.;Orebro Univ, Fac Med & Hlth, Dept Lab Med, Orebro, Sweden..
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2017 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 39, no 4, article id 697569Article in journal (Refereed) Published
Abstract [en]

Altered claudin expression has been described in colon, prostatic, ovarian, and breast carcinoma. However, the role of epigenetic modifications in these genes and their role in colorectal cancer is unknown. We aimed our study to investigate whether claudin protein expression and methylation of CLDN can influence the tumorigenesis of colorectal cancer. A total of 31 patients diagnosed with colorectal carcinoma was used in this study. Immunohistochemical staining was used to study protein expression in both tumor and the adjacent nonneoplastic mucosa of claudin 1, 4, and 7. To detect the DNA methylation pattern of CLDN1, 4, and 7, genomic DNA was extracted from both the tumor and the adjacent nonneoplastic mucosa. Methylation analysis was carried out using bisulfite pyrosequencing. Cell membrane staining intensity of all claudins was found significantly lower in colorectal cancer tissues when compared to paired normal mucosa (p = 0.001). For claudin 4, the percentage of cells staining positively was also significantly reduced (p = 0.04). In normal mucosa, cytoplasm showed no staining for claudins in any patient, whereas in paired colorectal cancer tissues, significant cytoplasmic staining appeared both for claudin 1 (p = 0.04) and claudin 4 (p = 0.01). Tumor samples were significantly hypomethylated in CLDN1 (p < 0.05). In conclusion, our results show that CLDN1 is significantly hypomethylated in tumor samples and that the membrane staining intensity for claudin 1, 4, and 7 is significantly lower in colorectal cancer tissues than in adjacent nonneoplastic tissue. Colorectal cancer cells showed dystopic cytoplasmic location of claudins.

Place, publisher, year, edition, pages
Sage Publications, 2017. Vol. 39, no 4, article id 697569
Keywords [en]
Tight junction, methylation, colon cancer, claudin
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-323664DOI: 10.1177/1010428317697569ISI: 000400268800047PubMedID: 28381183OAI: oai:DiVA.org:uu-323664DiVA, id: diva2:1112585
Available from: 2017-06-20 Created: 2017-06-20 Last updated: 2018-04-04Bibliographically approved

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