A1 Journal article (refereed)
Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis (2021)

Mäki-Nevala, S., Ukwattage, S., Wirta, E.-V., Ahtiainen, M., Ristimäki, A., Seppälä, T. T., Lepistö, A., Mecklin, J.-P., & Peltomäki, P. (2021). Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis. Biomolecules, 11(10), Article 1440. https://doi.org/10.3390/biom11101440

JYU authors or editors

Publication details

All authors or editors: Mäki-Nevala, Satu; Ukwattage, Sanjeevi; Wirta, Erkki-Ville; Ahtiainen, Maarit; Ristimäki, Ari; Seppälä, Toni T.; Lepistö, Anna; Mecklin, Jukka-Pekka; Peltomäki, Päivi

Journal or series: Biomolecules

eISSN: 2218-273X

Publication year: 2021

Volume: 11

Issue number: 10

Article number: 1440

Publisher: MDPI AG

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3390/biom11101440

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/78023


Immunological and epigenetic changes are interconnected and contribute to tumorigenesis. We determined the immunoprofiles and promoter methylation of inflammation-related genes for colitis-associated colorectal carcinomas (CA-CRC). The results were compared with Lynch syndrome (LS)-associated colorectal tumors, which are characterized by an active immune environment through inherited mismatch repair defects. CA-CRCs (n = 31) were immunohistochemically evaluated for immune cell scores (ICSs) and PDCD1 and CD274 expression. Seven inflammation-associated genes (CD274, NTSR1, PPARG, PTGS2, PYCARD, SOCS1, and SOCS2), the repair gene MGMT, and eight standard marker genes for the CpG Island Methylator Phenotype (CIMP) were investigated for promoter methylation in CA-CRCs, LS tumors (n = 29), and paired normal mucosae by multiplex ligation-dependent probe amplification. All but one CA-CRCs were microsatellite-stable and all LS tumors were microsatellite-unstable. Most CA-CRCs had a high ICS (55%) and a positive CD274 expression in immune cells (52%). NTSR1 revealed frequent tumor-specific hypermethylation in CA-CRC and LS. When compared to LS mucosae, normal mucosae from patients with CA-CRC showed significantly higher methylation of NTSR1 and most CIMP markers. In conclusion, CA-CRCs share a frequent ICShigh/CD274pos expression pattern with LS tumors. Elevated methylation in normal mucosa may indicate field cancerization as a feature of CA-CRC-associated tumorigenesis.

Keywords: bowel cancer; cancer of the large intestine; Lynch syndrome; inflammation; ulcerative colitis; immune response; epigenetics; DNA methylation

Free keywords: Lynch syndrome; ulcerative colitis; colon cancer; immune cell score; DNA methylation; inflammation-associated genes

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Ministry reporting: Yes

Preliminary JUFO rating: 1

Last updated on 2021-05-10 at 11:35