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Epithelial-Specific SHP1-P2 Methylation - a Novel Universal Tumor Marker for Detection of Colorectal Cancer Lymph Node Metastasis

  • Rattanatanyong, Prakasit (Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, Chulalongkorn University) ;
  • Keelawat, Somboon (Department of Pathology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital) ;
  • Kitkumthorn, Nakarin (Department of Oral Biology, Faculty of Dentistry, Mahidol University) ;
  • Mutirangura, Apiwat (Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, Chulalongkorn University)
  • Published : 2016.08.01

Abstract

Background: Methylation of promoter 2 of the SHP1 gene is epithelial cell specific, with reported potential as a lymph node metastatic marker. Objective: To demonstrate SHP1-P2 methylation-specific quantitative PCR effectiveness in detecting colorectal cancer (CRC) DNA in lymph nodes. Materials and Methods: SHP1-P2 methylation levels were measured in lymph nodes of CRC patients and compared with pathological findings and patient prognosis. Results: Lymph nodes of CRC metastatic patients without microscopically detectable cancer cells had higher SHP1-P2 methylation levels than lymph nodes of controls (p<0.001). In addition, a higher SHP1-P2 methylation level was associated with a shorter duration until adverse disease events, metastasis, recurrence and death (r2 = 0.236 and p value = 0.048). Studying two cohorts of 74 CRC patients without microscopic lymph node metastases showed that only the cohort containing samples with high SHP1-P2 methylation levels had a significant hazard ratio of 3.8 (95%CI = 1.02 to 14.2). Conclusions: SHP1-P2 methylation PCR can detect CRC DNA in lymph nodes even if cancer cells are not visible under a microscope, confirming applicability as a potential universal lymph node metastatic marker.

Keywords

Acknowledgement

Supported by : Thailand Research Fund

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