title: Response and toxicity prediction by MALDI-TOF-MS serum peptide profiling in patients with non-small cell lung cancer.
abstract: We validated a previously reported proteomic signature, associated with treatment outcome, in an independent cohort of patients with non-small cell lung cancer (NSCLC). A novel peptide signature was developed to predict toxicity.
  
  
  
  Using automated magnetic C18 bead-assisted serum peptide capture coupled to MALDI-TOF MS, we conducted serum peptide profiling of 50 NCSLC patients participating in a phase II trial of erlotinib and sorafenib. On the obtained peptide mass profiles, we applied a previously described proteomic classification algorithm. Additionally, associations between observed side effects and peptide profiles were investigated.
  
  
  
  Application of the previously acquired algorithm successfully classified the new cohort of patients in groups significantly associated with the outcome. The "poor" group exhibited shorter median progression-free survival (PFS) and overall survival (OS) of 1.35 and 1.98 months (with p = 0.00677 and p = 0.00002, respectively) while the "good" group had significantly longer PFS and OS (10.63 and 14.4 months with p = 0.00142 and p = 0.00002, respectively), compared to average OS and PFS. Two specific peptides were detected in the sera of all patients that developed severe toxicity.
  
  
  
  Our results provide an algorithm that, following prospective validation in larger cohorts, could assist treatment selection of patients with NSCLC in the first line setting.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Rovithi
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Joline S W
authors.initials: JS
authors.lastname: Lind
authors.affiliation: OncoProteomics Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Thang V
authors.initials: TV
authors.lastname: Pham
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Voortman
authors.affiliation: OncoProteomics Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jaco C
authors.initials: JC
authors.lastname: Knol
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.affiliation: OncoProteomics Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Connie R
authors.initials: CR
authors.lastname: Jimenez
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D010455:Peptides / Q000097:blood*; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D040901:Proteomics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D000077157:Sorafenib; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D010455:Peptides; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Cancer; EGFR prediction; Response; Serum proteomics; Toxicity