Expression of a novel CNPY2 isoform in colorectal cancer and its association with oncologic prognosis

Aging (Albany NY). 2017 Nov 13;9(11):2334-2351. doi: 10.18632/aging.101324.

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related mortality. Recently, we identified a novel biomarker, canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform2, and subsequently investigated its expression and prognostic value in CRC patients. We initially generated CNPY2 isoform2 monoclonal antibodies and examined CNPY2 isoform2 expression in CRC cell lines and tissues using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry analyses. We found that CNPY2 isoform2 expression significantly increased in tumor cell lines and tissues compared with that in normal colon epithelial cells and tumor-adjacent normal tissues. Survival analysis indicated that patients with low CNPY2 isoform2 expression had poorer 5-year overall survival (OS) in both the training cohort (41.7% vs. 77.7%, P = 0.007) and validation cohort (47.1% vs. 78.8%, P = 0.002). In multivariable analysis, CNPY2 isoform2 was identified as a predictor of 5-year OS in both the training cohort [hazard ratio (HR) = 5.001; 95% confidence interval (CI) 2.156-11.598, P < 0.001) and validation cohort (HR= 2.443; 95% CI 1.197- 4.983, P = 0.014). In conclusion, CNPY2 isoform2 represents as a novel and valuable prognostic indicator for CRC patients, while the oncologic function of CNPY2 requires further study.

Keywords: CNPY2 isoform2; colorectal cancer; expression; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Chi-Square Distribution
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • HT29 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Protein Isoforms
  • Risk Factors
  • Time Factors

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CNPY2 protein, human
  • Protein Isoforms