1. Immunoprofiles and DNA methylation of inflammatory marker genes in ulcerative colitis-associated colorectal tumorigenesis
- Author
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Anna Lepistö, Jukka-Pekka Mecklin, Toni T. Seppälä, Erkki Ville Wirta, Ari Ristimäki, Päivi Peltomäki, Maarit Ahtiainen, Sanjeevi Ukwattage, Satu Mäki-Nevala, Tampere University, Department of Gastroenterology, Department of Medical and Clinical Genetics, Department of Pathology, HUSLAB, HUS Diagnostic Center, ATG - Applied Tumor Genomics, HUS Abdominal Center, and II kirurgian klinikka
- Subjects
Male ,Carcinogenesis ,medicine.disease_cause ,Biochemistry ,0302 clinical medicine ,Intestinal Mucosa ,DNA Modification Methylases ,0303 health sciences ,MUCOSA ,DNA methylation ,tulehdus ,inflammation-associated genes ,PYCARD ,Methylation ,Middle Aged ,Lynch syndrome ,QR1-502 ,EPIGENETICS ,3. Good health ,DNA-metylaatio ,Gene Expression Regulation, Neoplastic ,Phenotype ,colon cancer ,epigenetiikka ,030220 oncology & carcinogenesis ,immuunivaste ,Female ,Colorectal Neoplasms ,CANCERS ,INSTABILITY ,suolistosyövät ,Biology ,3121 Internal medicine ,Microbiology ,Article ,03 medical and health sciences ,medicine ,Humans ,Epigenetics ,Lynchin oireyhtymä ,Molecular Biology ,neoplasms ,030304 developmental biology ,paksusuolisyöpä ,ulcerative colitis ,Inflammation ,CpG Island Methylator Phenotype ,Tumor Suppressor Proteins ,haavainen koliitti ,medicine.disease ,3126 Surgery, anesthesiology, intensive care, radiology ,digestive system diseases ,DNA Repair Enzymes ,3121 General medicine, internal medicine and other clinical medicine ,Mutation ,immune cell score ,Cancer research ,1182 Biochemistry, cell and molecular biology ,Colitis, Ulcerative ,CpG Islands ,Field cancerization ,Biomarkers - Abstract
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.
- Published
- 2021