Background: Carcinogenesis of colorectal cancer (CRC) is influenced greatly by the canonical WNT signaling pathway. Genetically, the secreted protein Dickkopf (Dkk) family is known as an antagonist to the WNT. To clarify the role of DKK1 in the WNT signaling pathway in the colorectal carcinogenesis, we examined the DKK1 promoter methylation in CRC and analyze the relationship of expression level of DKK1 and MYC in relation with APC gene abnormalities. Methods: We integrated clinico-pathological and molecular findings of 41 cases of CRC. We adopted methylation-specific PCR, DNA sequencing, allelic loss analysis, quantitative RT-PCR, and MSI testing for genetic analyses. Results: CRCs with DKK1 promotor methylation were found in 10 cases (24.4%), which were located predominantly in the proximal colon and frequently showed findings of poorly differentiated adenocarcinoma or mucinous adenocarcinoma. Furthermore, colorectal cancers with DKK1 promotor methylation showed characteristics of microsatellite instability (MSI)-high (70%) and a BRAF mutation (40%), which are known as the CpG island methylator phenotype (CIMP). In the DKK1 promotor methylation group, the relative expression level of DKK1 mRNA was significantly reduced in comparison to the DKK1 promotor un-methylation group (p < 0.05). When excluding the impact of APC abnormality, MYC expression in the DKK1 promotor methylation group was significantly elevated compared to that in the DKK1 promotor un-methylation group (p < 0.05). Conclusions: It is suggested that DKK1 is one of the regulators involved in MYC expression through the WNT signaling pathway and may have a negative effect on carcinogenesis of the colorectum without APC abnormalities.
| Published in | International Journal of Gastroenterology (Volume 6, Issue 1) |
| DOI | 10.11648/j.ijg.20220601.13 |
| Page(s) | 9-17 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2022. Published by Science Publishing Group |
DKK1, MYC, WNT Signaling Pathway, Methylation, Colorectal Cancer, CIMP
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APA Style
Mie Yoshimura, Kazuo Tamura, Tomoki Yamano, Nagahide Matsubara, Akihito Babaya, et al. (2022). DKK1 Promoter Methylation in Colorectal Cancer Is Associated with CIMP and Elevation of MYC Expression. International Journal of Gastroenterology, 6(1), 9-17. https://doi.org/10.11648/j.ijg.20220601.13
ACS Style
Mie Yoshimura; Kazuo Tamura; Tomoki Yamano; Nagahide Matsubara; Akihito Babaya, et al. DKK1 Promoter Methylation in Colorectal Cancer Is Associated with CIMP and Elevation of MYC Expression. Int. J. Gastroenterol. 2022, 6(1), 9-17. doi: 10.11648/j.ijg.20220601.13
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author = {Mie Yoshimura and Kazuo Tamura and Tomoki Yamano and Nagahide Matsubara and Akihito Babaya and Michiko Yasuhara and Aya Yano and Miki Fukumoto and Norihito Kawashita and Junko Tatsumi-Miyajima and Naohiro Tomita},
title = {DKK1 Promoter Methylation in Colorectal Cancer Is Associated with CIMP and Elevation of MYC Expression},
journal = {International Journal of Gastroenterology},
volume = {6},
number = {1},
pages = {9-17},
doi = {10.11648/j.ijg.20220601.13},
url = {https://doi.org/10.11648/j.ijg.20220601.13},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijg.20220601.13},
abstract = {Background: Carcinogenesis of colorectal cancer (CRC) is influenced greatly by the canonical WNT signaling pathway. Genetically, the secreted protein Dickkopf (Dkk) family is known as an antagonist to the WNT. To clarify the role of DKK1 in the WNT signaling pathway in the colorectal carcinogenesis, we examined the DKK1 promoter methylation in CRC and analyze the relationship of expression level of DKK1 and MYC in relation with APC gene abnormalities. Methods: We integrated clinico-pathological and molecular findings of 41 cases of CRC. We adopted methylation-specific PCR, DNA sequencing, allelic loss analysis, quantitative RT-PCR, and MSI testing for genetic analyses. Results: CRCs with DKK1 promotor methylation were found in 10 cases (24.4%), which were located predominantly in the proximal colon and frequently showed findings of poorly differentiated adenocarcinoma or mucinous adenocarcinoma. Furthermore, colorectal cancers with DKK1 promotor methylation showed characteristics of microsatellite instability (MSI)-high (70%) and a BRAF mutation (40%), which are known as the CpG island methylator phenotype (CIMP). In the DKK1 promotor methylation group, the relative expression level of DKK1 mRNA was significantly reduced in comparison to the DKK1 promotor un-methylation group (p MYC expression in the DKK1 promotor methylation group was significantly elevated compared to that in the DKK1 promotor un-methylation group (p Conclusions: It is suggested that DKK1 is one of the regulators involved in MYC expression through the WNT signaling pathway and may have a negative effect on carcinogenesis of the colorectum without APC abnormalities.},
year = {2022}
}
TY - JOUR T1 - DKK1 Promoter Methylation in Colorectal Cancer Is Associated with CIMP and Elevation of MYC Expression AU - Mie Yoshimura AU - Kazuo Tamura AU - Tomoki Yamano AU - Nagahide Matsubara AU - Akihito Babaya AU - Michiko Yasuhara AU - Aya Yano AU - Miki Fukumoto AU - Norihito Kawashita AU - Junko Tatsumi-Miyajima AU - Naohiro Tomita Y1 - 2022/05/12 PY - 2022 N1 - https://doi.org/10.11648/j.ijg.20220601.13 DO - 10.11648/j.ijg.20220601.13 T2 - International Journal of Gastroenterology JF - International Journal of Gastroenterology JO - International Journal of Gastroenterology SP - 9 EP - 17 PB - Science Publishing Group SN - 2640-169X UR - https://doi.org/10.11648/j.ijg.20220601.13 AB - Background: Carcinogenesis of colorectal cancer (CRC) is influenced greatly by the canonical WNT signaling pathway. Genetically, the secreted protein Dickkopf (Dkk) family is known as an antagonist to the WNT. To clarify the role of DKK1 in the WNT signaling pathway in the colorectal carcinogenesis, we examined the DKK1 promoter methylation in CRC and analyze the relationship of expression level of DKK1 and MYC in relation with APC gene abnormalities. Methods: We integrated clinico-pathological and molecular findings of 41 cases of CRC. We adopted methylation-specific PCR, DNA sequencing, allelic loss analysis, quantitative RT-PCR, and MSI testing for genetic analyses. Results: CRCs with DKK1 promotor methylation were found in 10 cases (24.4%), which were located predominantly in the proximal colon and frequently showed findings of poorly differentiated adenocarcinoma or mucinous adenocarcinoma. Furthermore, colorectal cancers with DKK1 promotor methylation showed characteristics of microsatellite instability (MSI)-high (70%) and a BRAF mutation (40%), which are known as the CpG island methylator phenotype (CIMP). In the DKK1 promotor methylation group, the relative expression level of DKK1 mRNA was significantly reduced in comparison to the DKK1 promotor un-methylation group (p MYC expression in the DKK1 promotor methylation group was significantly elevated compared to that in the DKK1 promotor un-methylation group (p Conclusions: It is suggested that DKK1 is one of the regulators involved in MYC expression through the WNT signaling pathway and may have a negative effect on carcinogenesis of the colorectum without APC abnormalities. VL - 6 IS - 1 ER -
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