Circulating Carnosine Dipeptidase 1 Associates With Weight Loss and Poor Prognosis in Gastrointestinal Cancer

PLoS One. 2015 Apr 21;10(4):e0123566. doi: 10.1371/journal.pone.0123566. eCollection 2015.

Abstract

Background: Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.

Design/subjects: Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer.

Results: Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results.

Conclusions: In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / blood*
  • Cachexia / blood*
  • Cachexia / mortality
  • Cachexia / pathology
  • Cohort Studies
  • Dipeptidases / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • CNDP1 protein, human
  • Dipeptidases

Grant support

This work was supported by grants from the Swedish Heart and Lung Foundation, the Swedish Diabetes Association, the Novo Nordisk Foundation, the Swedish Cancer Foundation, DiabetesWellness, the Swedish Medical Association, the Swedish Research Council, the Strategic Research Programme in Diabetes at the Karolinska Institute, the Knut and Alice Wallenberg Foundation and SciLifeLab Stockholm. None of the funding sources have taken part in planning, performing, analyzing the data or writing the manuscript.