DNA hypermethylation as a predictor of extramural vascular invasion (EMVI) in rectal cancer
Autor: | Gareth J.S. Jenkins, John Beynon, A. Paul Griffiths, Dean A. Harris, Jeremy Williamson, Namor Williams, HG Jones, Rory Kokelaar |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Male
Cancer Research Colorectal cancer Dna hypermethylation Kaplan-Meier Estimate Disease-Free Survival Vascular invasion Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Medicine Humans Neoplasm Invasiveness Epigenetics Prospective Studies Aged Pharmacology Aged 80 and over Neovascularization Pathologic business.industry Extramural Rectal Neoplasms Rectum Promoter DNA Neoplasm DNA Methylation Middle Aged medicine.disease Oncology CpG site 030220 oncology & carcinogenesis Cancer research Molecular Medicine 030211 gastroenterology & hepatology Original Article CpG Islands Female business Follow-Up Studies |
Popis: | DNA hypermethylation in gene promoter regions (CpG islands) is emerging as an important pathway in colorectal cancer tumourigenesis. Whilst genetic mutations have been associated with extramural vascular invasion (EMVI) in rectal cancer, no such association has yet been made with epigenetic factors.100 consecutive neoadjuvant-naïve patients undergoing curative surgery for rectal were classified according to the presence or absence of EMVI on histopathological examination. DNA was extracted from tumours and subjected to bisulfite conversion and methylation-specific PCR to determine CIMP status (high, intermediate, or low; according to a validated panel of 8 genes). CIMP status was correlated with EMVI status, histopathological, clinical, and demographic variables, in addition to overall (OS) and disease free (DFS) survival.51 patients were characterised as CIMP-low, 48 CIMP-intermediate, and one patient CIMP-high. EMVI-positivity was associated with CIMP-intermediate epigenotype (p0.001). Patients with EMVI-positive tumours were found to have significantly more advanced disease by pT, pN, and pAJCC categorisation (p = 0.002, p0.001, and = p0.001, respectively). EMVI-positivity was significantly associated with the requirement for adjuvant chemotherapy (p0.001), and worse DFS but not OS (p = 0.012 and p = 0.052).Given the association between CIMP-intermediate epigenotype and EMVI-positivity, and the subsequent disadvantage in pathological stage, requirement for adjuvant therapy and worse survival, tumour epigenotyping could potentially play an important role in personalising patients' cancer care. Further work is required to understand the mechanisms that underlie the observed effect, with the hope that they may provide novel opportunities for intervention and inform treatment decisions in rectal cancer. |
Databáze: | OpenAIRE |
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