title: Clinical predictive circulating peptides in rectal cancer patients treated with neoadjuvant chemoradiotherapy.
abstract: Preoperative chemoradiotherapy is worldwide accepted as a standard treatment for locally advanced rectal cancer. Current standard of treatment includes administration of ionizing radiation for 45-50.4 Gy in 25-28 fractions associated with 5-fluorouracil administration during radiation therapy. Unfortunately, 40% of patients have a poor or absent response and novel predictive biomarkers are demanding. For the first time, we apply a novel peptidomic methodology and analysis in rectal cancer patients treated with preoperative chemoradiotherapy. Circulating peptides (Molecular Weight <3 kDa) have been harvested from patients' plasma (n = 33) using nanoporous silica chip and analyzed by Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometer. Peptides fingerprint has been compared between responders and non-responders. Random Forest classification selected three peptides at m/z 1082.552, 1098.537, and 1104.538 that were able to correctly discriminate between responders (n = 16) and non-responders (n = 17) before therapy (T0) providing an overall accuracy of 86% and an area under the receiver operating characteristic (ROC) curve of 0.92. In conclusion, the nanoporous silica chip coupled to mass spectrometry method was found to be a realistic method for plasma-based peptide analysis and we provide the first list of predictive circulating biomarker peptides in rectal cancer patients underwent preoperative chemoradiotherapy.
authors.affiliation: Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico, IRCCS National Cancer Institute, Aviano (PN), Italy; Istituto di Ricerca Pediatrica- Citt, à,, della Speranza, Corso Stati Uniti 4, Padova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Crotti
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Enzo
authors.forename: Chiara
authors.initials: C
authors.lastname: Bedin
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pucciarelli
authors.forename: Isacco
authors.initials: I
authors.lastname: Maretto
authors.forename: Paola
authors.initials: P
authors.lastname: Del Bianco
authors.forename: Pietro
authors.initials: P
authors.lastname: Traldi
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Marco
authors.initials: M
authors.lastname: Agostini
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D059248:Chemoradiotherapy; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008297:Male; D008875:Middle Aged; D036103:Nanotechnology / Q000379:methods*; D020360:Neoadjuvant Therapy; D010455:Peptides / Q000097:blood; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000097:blood* / Q000628:therapy; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D010455:Peptides