6533b861fe1ef96bd12c4fb0

RESEARCH PRODUCT

Immunoprofiles and DNA methylation of inflammatory marker genes in ulcerative colitis-associated colorectal tumorigenesis

Anna LepistöJukka-pekka MecklinToni T. SeppäläErkki Ville WirtaAri RistimäkiPäivi PeltomäkiMaarit AhtiainenSanjeevi UkwattageSatu Mäki-nevala

subject

MaleCarcinogenesismedicine.disease_causeBiochemistry0302 clinical medicineIntestinal MucosaDNA Modification Methylases0303 health sciencesMUCOSADNA methylationtulehdusinflammation-associated genesPYCARDMethylationMiddle AgedLynch syndromeQR1-502EPIGENETICS3. Good healthDNA-metylaatioGene Expression Regulation NeoplasticPhenotypecolon cancerepigenetiikka030220 oncology & carcinogenesisimmuunivasteDNA methylationFemaleColorectal NeoplasmsCANCERSINSTABILITYsuolistosyövätBiology3121 Internal medicineMicrobiologyArticle03 medical and health sciencesmedicineHumansEpigeneticsLynchin oireyhtymäMolecular Biologyneoplasms030304 developmental biologypaksusuolisyöpäulcerative colitisInflammationCpG Island Methylator PhenotypeTumor Suppressor Proteinshaavainen koliittimedicine.disease3126 Surgery anesthesiology intensive care radiologydigestive system diseasesDNA Repair EnzymesLynch syndrome3121 General medicine internal medicine and other clinical medicineMutationimmune cell scoreCancer research1182 Biochemistry cell and molecular biologyColitis UlcerativeCpG IslandsField cancerizationCarcinogenesisBiomarkers

description

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.

yearjournalcountryeditionlanguage
2021-09-30
10.3390/biom11101440https://trepo.tuni.fi/handle/10024/135286