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Article

Tumor p16INK4 gene expression and prognosis in colorectal cancer

  • Authors:
    • Hirotaka Kitamura
    • Hirofumi Takemura
    • Toshinari Minamoto
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterological Surgery, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa 920‑8530, Japan, Department of General and Cardiothoracic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920‑0934, Japan, Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920‑0934, Japan
  • Pages: 1367-1376
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    Published online on: November 26, 2018
       https://doi.org/10.3892/or.2018.6884
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Abstract

Hypermethylation of the tumor suppressor gene p16INK4 (p16) promoter is associated with worse prognosis in colorectal cancer (CRC). In the present study, it was investigated whether p16 mRNA expression correlates with the methylation of its promoter, and whether it influences prognosis in patients with CRC. DNA and RNA were extracted from 101 resected tumor specimens. A MethyLight assay was used to quantify p16 methylation in terms of percentage of methylated reference (PMR), and the expression of p16 mRNA was measured using reverse transcription‑polymerase chain reaction. Associations between p16 methylation or mRNA expression and patient survival were evaluated using Kaplan‑Meier analysis and Cox proportional hazards regression. p16 methylation was detected in 67 cases (66.3%) and the median PMR value was 0.344 (range, 0.00‑468.6). Using a cut‑off PMR value of 4, high p16 methylation was observed in 18 cases (17.8%). No significant association was observed between p16 methylation level and patient prognosis. As expected, a significant inverse association was observed between p16 methylation and mRNA expression (P=0.034). Amongst the 83 cases with low p16 methylation, a significantly worse outcome was identified in patients expressing high p16 mRNA expression levels (P=0.026). Multivariate analysis identified that p16 mRNA expression was an independent prognostic factor for worse survival (P=0.011). These results suggested a paradoxical association between high levels of p16 mRNA expression in the tumor and worse prognosis in patients with CRC.
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Copy and paste a formatted citation
Spandidos Publications style
Kitamura H, Takemura H and Minamoto T: Tumor p16INK4 gene expression and prognosis in colorectal cancer. Oncol Rep 41: 1367-1376, 2019.
APA
Kitamura, H., Takemura, H., & Minamoto, T. (2019). Tumor p16INK4 gene expression and prognosis in colorectal cancer. Oncology Reports, 41, 1367-1376. https://doi.org/10.3892/or.2018.6884
MLA
Kitamura, H., Takemura, H., Minamoto, T."Tumor p16INK4 gene expression and prognosis in colorectal cancer". Oncology Reports 41.2 (2019): 1367-1376.
Chicago
Kitamura, H., Takemura, H., Minamoto, T."Tumor p16INK4 gene expression and prognosis in colorectal cancer". Oncology Reports 41, no. 2 (2019): 1367-1376. https://doi.org/10.3892/or.2018.6884
Copy and paste a formatted citation
x
Spandidos Publications style
Kitamura H, Takemura H and Minamoto T: Tumor p16INK4 gene expression and prognosis in colorectal cancer. Oncol Rep 41: 1367-1376, 2019.
APA
Kitamura, H., Takemura, H., & Minamoto, T. (2019). Tumor p16INK4 gene expression and prognosis in colorectal cancer. Oncology Reports, 41, 1367-1376. https://doi.org/10.3892/or.2018.6884
MLA
Kitamura, H., Takemura, H., Minamoto, T."Tumor p16INK4 gene expression and prognosis in colorectal cancer". Oncology Reports 41.2 (2019): 1367-1376.
Chicago
Kitamura, H., Takemura, H., Minamoto, T."Tumor p16INK4 gene expression and prognosis in colorectal cancer". Oncology Reports 41, no. 2 (2019): 1367-1376. https://doi.org/10.3892/or.2018.6884
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