ArticleJournal of cancer research and clinical oncology2010
Aberrant p16((INK4a)) methylation is a frequent event in colorectal cancers: prognostic value and relation to mRNA expression and immunoreactivity.
Article in Journal of cancer research and clinical oncology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review.Clinical epigenetics · 2018Pooled it
- Pooled it
- DNA Methylation and Transcript Variant Analysis ofInternational journal of molecular sciences · 2025Article
- Pathogenesis and biomarkers of colorectal cancer by epigenetic alteration.Intestinal research · 2024Review
- Epigenetic Landscape of Liquid Biopsy in Colorectal Cancer.Frontiers in cell and developmental biology · 2021Review
- Epigenetics of colorectal cancer: biomarker and therapeutic potential.Nature reviews. Gastroenterology & hepatology · 2020Review
- Detection of Differentially Methylated Regions Using Bayes Factor for Ordinal Group Responses.Genes · 2019Article
- PBX3 hypermethylation in peripheral blood leukocytes predicts better prognosis in colorectal cancer: A propensity score analysis.Cancer medicine · 2019Article
- The hypermethylation of p16 gene exon 1 and exon 2: potential biomarkers for colorectal cancer and are associated with cancer pathological staging.BMC cancer · 2018Article
- Hypermethylation of CDKN2A exon 2 in tumor, tumor-adjacent and tumor-distant tissues from breast cancer patients.BMC cancer · 2017Article
- DNA methylation patterns as noninvasive biomarkers and targets of epigenetic therapies in colorectal cancer.Epigenomics · 2016Review
- Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers.Gastroenterology · 2015Review
- Combined methylation of p16 and hMLH1 (CMETH2) discriminates a subpopulation with better prognosis in colorectal cancer patients with microsatellite instability tumors.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- DNA methylation combinations in adjacent normal colon tissue predict cancer recurrence: evidence from a clinical cohort study.PloS one · 2015Article
- Preoperative low dose NSAID treatment influences the genes for stemness, growth, invasion and metastasis in colorectal cancer.International journal of oncology · 2014Article
- Promoter region hypermethylation and mRNA expression of MGMT and p16 genes in tissue and blood samples of human premalignant oral lesions and oral squamous cell carcinoma.BioMed research international · 2014Article
- The in situ local immune response, tumour senescence and proliferation in colorectal cancer.British journal of cancer · 2013Article
- Clinical correlates of promoter hypermethylation of four target genes in head and neck cancer: a cooperative group correlative study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- A study of the frequency of methylation of gene promoter regions in colorectal cancer in the Taiwanese population.Journal of genetics · 2013Article
- Epigenetic changes in colorectal cancer.Chinese journal of cancer · 2013Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAberrant p16((INK4a)) promoter methylation is common in colorectal cancer (CRC), but its clinicopathological significance remains controversial. The present study was therefore conducted to analyze p16((INK4a)) methylation and its relationship to clinicopathological features, mRNA levels and immunoreactivity in a series of lesions.
methodsp16((INK4a)) methylation was assessed for normal mucosa (n = 30) and CRC samples (n = 212) by methylation-specific real-time quantitative PCR, and p16((INK4a)) expression by immunostaining in formalin-fixed paraffin-embedded specimens. In addition, fresh DNA (n = 61) was analyzed for relationships to p16((INK4a)) mRNA by reverse-transcription PCR.
resultsThe p16((INK4a)) methylation index of normal mucosa samples ranged from 0 to 2% (mean, 0.23%; median, 0.02%), while the values for tumor samples varied widely from 0 to 100% (mean, 25.7%; median, 7.1%), the difference being statistically significant (P < 0.001). Of 151 paraffin-embedded CRC tissue samples, 51 (34%), 54 (36%), and 46 (30%) were classified as low, intermediate, and high for aberrant methylation of p16((INK4a)). High p16((INK4a)) methylation was significantly associated with large tumor size (P = 0.025). Patients with higher methylation further showed more frequent recurrence as compared with the low-methylation group, and shortened cancer-related survival (Hazard ratio [HR], 3.379; P < 0.001) and recurrence-free survival (HR, 3.962; P < 0.001 on multivariate analysis). A significant inverse relationship was apparent between the p16((INK4a)) methylation and immunoreactivity (P = 0.017). A similar tendency was also observed for the methylation status and the mRNA level (P = 0.195).
conclusionsWe conclude that p16((INK4a)) methylation results in transcriptional silencing and defines a group of CRCs with a poor prognosis.
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