title: Expression of claudin 1, claudin 4, and claudin 7 in colorectal cancer and its relation with CLDN DNA methylation patterns.
abstract: 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.
authors.affiliation: 1 Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Victoria
authors.initials: V
authors.lastname: Hahn-Strömberg
authors.affiliation: 2 Department of Clinical Research, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Shlear
authors.initials: S
authors.lastname: Askari
authors.affiliation: 2 Department of Clinical Research, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Abrar
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: 2 Department of Clinical Research, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.|3 Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Rahel
authors.initials: R
authors.lastname: Befekadu
authors.affiliation: 4 Division of Clinical Chemistry, Department of Medical Biosciences, Umeå University, Umeå, Sweden.
authors.forename: Torbjörn K
authors.initials: TK
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D000368:Aged; D062445:Claudin-1 / Q000032:analysis / Q000235:genetics*; D062506:Claudin-4 / Q000032:analysis / Q000235:genetics*; D057167:Claudins / Q000032:analysis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged
chemical_list: C568108:CLDN1 protein, human; C568157:CLDN4 protein, human; C473255:CLDN7 protein, human; D062445:Claudin-1; D062506:Claudin-4; D057167:Claudins
keywords: Tight junction; claudin; colon cancer; methylation