PBX3 hypermethylation in peripheral blood leukocytes predicts better prognosis in colorectal cancer: A propensity score analysis

Cancer Med. 2019 Jul;8(8):4001-4011. doi: 10.1002/cam4.2321. Epub 2019 May 29.

Abstract

Objective: The significance of gene methylation in peripheral blood leukocytes (PBLs) for assessing cancer prognosis is poorly understood. Our purpose is to assess the association between PBX3 methylation in PBLs and colorectal cancer (CRC) prognosis.

Methods: A total of 369 CRC patients were followed up for up to 10 years in this cohort study. PBL PBX3 methylation levels were determined by methylation-sensitive high-resolution melting. Cox regression models and Log-rank tests were used to analyze the associations between PBX3 methylation status and CRC prognosis with a propensity score (PS) method to control confounding biases.

Results: In this study, we found that CRC patients with PBL PBX3 hypermethylation status had a better overall survival (OS) (hazard ratio [HRPS-adjusted ], 0.72 [95% CI, 0.52-1.00]; P = 0.049). Subgroup analyses showed that the beneficial effect of PBX3 hypermethylation status on CRC 10-years OS remained significant among UICC stage III patients ([HRPS-adjusted ], 0.60 [95% CI, 0.38 to 0.95]; P = 0.029) and colon cancer patients ([HRPS-adjusted ], 0.49 [95% CI, 0.26 to 0.92]; P = 0.027).

Conclusion: PBL PBX3 hypermethylation is positively associated with better prognosis of CRC, especially for the UICC stage III CRC patients and colon cancer patients.

Keywords: PBX3; DNA methylation; colorectal cancer; peripheral blood leukocyte; predictive biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Female
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Leukocytes / metabolism*
  • Male
  • Methylation
  • Middle Aged
  • Prognosis
  • Propensity Score
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism

Substances

  • Homeodomain Proteins
  • Proto-Oncogene Proteins
  • proto-oncogene protein Pbx3