Gene pair based prognostic signature for colorectal colon cancer

Medicine (Baltimore). 2018 Oct;97(42):e12788. doi: 10.1097/MD.0000000000012788.

Abstract

Background: The identification of high-risk colorectal cancer (CRC) patient is key to individualized treatment after surgery and reliable prognostic biomarkers are needed identifying high-risk CRC patients.

Methods: We developed a gene pair based prognostic signature that could can the prognosis risk in patients with CRC. This study retrospectively analyzed 4 public CRC datasets, and 1123 patients with CRC were divided into a training cohort (n = 300) and 3 independent validation cohorts (n = 507, 226, and 90 patients).

Results: A signature of 9 prognosis-related gene pairs (PRGPs) consisting of 17 unique genes was constructed. Then, a PRGP index (PRGPI) was constructed and divided patients into high- and low-risk groups according to the signature score. Patients in the high-risk group showed a poorer relapse-free survival than the low-risk group in both the training cohort [hazard ratio (HR) range, 4.6, 95% confidence interval (95% CI), 2.55-8.32; P < .0001] and meta-validation set (hazard ratio range, 4.09, 95% CI, 1.99-8.39; P < .0001). The PRGPI signature achieved a higher accuracy [mean concordance index (C-index): 0.6∼0.74] than a commercialized molecular signature (mean C-index, 0.48∼0.56) for estimation of relapse-free survival in comparable validation sets.

Conclusion: The gene pair based prognostic signature is a promising biomarker for estimating relapse-free survival of CRC.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / mortality
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Transcriptome / genetics*

Substances

  • Biomarkers, Tumor