title: Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.affiliation: Affinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Box 1031, 171 21, Solna, Sweden.
authors.forename: Frauke
authors.initials: F
authors.lastname: Henjes
authors.affiliation: Affinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Box 1031, 171 21, Solna, Sweden.
authors.forename: Jochen M
authors.initials: JM
authors.lastname: Schwenk
authors.affiliation: Affinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Box 1031, 171 21, Solna, Sweden.
authors.forename: Spyros
authors.initials: S
authors.lastname: Darmanis
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Department of Surgery, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Iresjö
authors.affiliation: Department of Surgery, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Naredi
authors.affiliation: Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Södersjukhuset, 118 83, Stockholm, Sweden.
authors.forename: Thorhallur
authors.initials: T
authors.lastname: Agustsson
authors.affiliation: Department of Surgery, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
authors.forename: Kent
authors.initials: K
authors.lastname: Lundholm
authors.affiliation: Affinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Box 1031, 171 21, Solna, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002100:Cachexia / Q000097:blood* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D004150:Dipeptidases / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C522928:CNDP1 protein, human; D004150:Dipeptidases