title: Development of a metabolites risk score for one-year mortality risk prediction in pancreatic adenocarcinoma patients.
abstract: OBJECTIVE
  Survival among patients with adenocarcinoma pancreatic cancer (PDCA) is highly variable, which ranges from 0% to 20% at 5 years. Such a wide range is due to tumor size and stage, as well other patients' characteristics. We analyzed alterations in the metabolomic profile, of PDCA patients, which are potentially predictive of patient's one-year mortality.
  
  
  METHODS
  A targeted metabolomic assay was conducted on serum samples of patients diagnosed with pancreatic cancer. Statistical analyses were performed only for those 27 patients with information on vital status at follow-up and baseline clinical features. Random Forest analysis was performed to identify all metabolites and clinical variables with the best capability to predict patient's mortality risk at one year. Regression coefficients were estimated from multivariable Weibull survival model, which included the most associated metabolites. Such coefficients were used as weights to build a metabolite risk score (MRS) which ranged from 0 (lowest mortality risk) to 1 (highest mortality risk). The stability of these weights were evaluated performing 10,000 bootstrap resamplings.
  
  
  RESULTS
  MRS was built as a weighted linear combination of the following five metabolites: Valine (HR = 0.62, 95%CI: 0.11-1.71 for each standard deviation (SD) of 98.57), Sphingomyeline C24:1 (HR = 2.66, 95%CI: 1.30-21.09, for each SD of 20.67), Lysine (HR = 0.36, 95%CI: 0.03-0.77, for each SD of 51.73), Tripentadecanoate TG15 (HR = 0.25, 95%CI: 0.01-0.82, for each SD of 2.88) and Symmetric dimethylarginine (HR = 2.24, 95%CI: 1.28-103.08, for each SD of 0.62), achieving a very high discrimination ability (survival c-statistic of 0.855, 95%CI: 0.816-0.894). Such association was still present even after adjusting for the most associated clinical variables (confounders).
  
  
  CONCLUSIONS
  The mass spectrometry-based metabolomic profiling of serum represents a valid tool for discovering novel candidate biomarkers with prognostic ability to predict one-year mortality risk in patients with pancreatic adenocarcinoma.
authors: Unit of Biostatistics I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy.
authors: Andrea
authors: A
authors: Fontana
authors: Unit of Biostatistics I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy.
authors: Massimiliano
authors: M
authors: Copetti
authors: Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), San Michele all'Adige, Italy.
authors: Iole Maria
authors: IM
authors: Di Gangi
authors: Unit of Bioinformatics, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy.
authors: Tommaso
authors: T
authors: Mazza
authors: Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy.
authors: Francesca
authors: F
authors: Tavano
authors: Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy.
authors: Domenica
authors: D
authors: Gioffreda
authors: Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), San Michele all'Adige, Italy.
authors: Fulvio
authors: F
authors: Mattivi
authors: Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy.
authors: Angelo
authors: A
authors: Andriulli
authors: Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), San Michele all'Adige, Italy.
authors: Urska
authors: U
authors: Vrhovsek
authors: Gastroenterology Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy.
authors: Valerio
authors: V
authors: Pazienza
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: multiple risk score; pancreatic cancer