Еxpression of claudin-1, 3, and 4 in colorectal cancer and polyps

Нефедова, Н.А.; Kharlova, O A; Malkov, P.G.

doi:10.17116/patol201678311-19

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(2 citation statements)

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Section: Introductionmentioning

confidence: 99%

“…There are, however, several studies on gene and protein expression of claudins in CRC; several of the studies promoting different claudins as tumor markers bring up-or downregulated and/or having an abnormal protein expression pattern compared to the adjacent nonneoplastic mucosa (ANNM). [5][6][7] Recently, we investigated the CLDN gene for polymorphisms and expression analysis that were associated with an increasing risk of CRC development, 8 making it interesting to study the DNA methylation pattern in CLDN1, 4, and 7 in CRC and find out whether there is any relation with claudin expression levels and/ or other clinical parameters. Since this group of genes has been implicated in tight junctions (TJs) disruption in several cancer forms, we hypothesized that CLDN1, 4, and 7 could be epigenetically changed in CRC.…”

Section: Introductionmentioning

confidence: 99%

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Expression of claudin 1, claudin 4, and claudin 7 in colorectal cancer and its relation with CLDN DNA methylation patterns

et al. 2017

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IntroductionTargeting tumor suppressor genes by epigenetic silencing especially in the promotor region is one of the probable mechanisms of carcinogenesis. 1 However, differential methylation may also occur outside of the promoter region and previous studies have shown that gene expression and tissue differentiation are powerfully affected by such methylation sites. 1,2 So far, there are limited data available on claudin (CLDN), epigenetics, and the relation to claudin protein expression as well as its role in the development of colorectal carcinoma (CRC). While DNA methylation of claudin 6 has been shown to be involved in the invasion of breast cancer cells 3 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.

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Section: Introductionmentioning

confidence: 99%