title: Exosomal proteins as prognostic biomarkers in non-small cell lung cancer.
abstract: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection for optimal treatment. We here evaluate exosomes by protein phenotyping as a prognostic biomarker in NSCLC.
  
  
  
  Exosomes from plasma of 276 NSCLC patients were phenotyped using the Extracellular Vesicle Array; 49 antibodies captured the proteins on the exosomes, and a cocktail of biotin-conjugated antibodies binding the general exosome markers CD9, CD81 and CD63 was used to visualise the captured exosomes. For each individual membrane-bound protein, results were analysed based on presence, in a concentration-dependent manner, and correlated to overall survival (OS).
  
  
  
  The 49 proteins attached to the exosomal membrane were evaluated. NY-ESO-1, EGFR, PLAP, EpCam and Alix had a significant concentration-dependent impact on inferior OS. Due to multiple testing, NY-ESO-1 was the only marker that maintained a significant impact on inferior survival (hazard rate (HR) 1.78 95% (1.78-2.44); p = 0.0001) after Bonferroni correction. Results were adjusted for clinico-pathological characteristics, stage, histology, age, sex and performance status.
  
  
  
  We illustrate the promising aspects associated with the use of exosomal membrane-bound proteins as a biomarker and demonstrate that they are a strong prognostic biomarker in NSCLC.
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. Electronic address: birgne@rm.dk.
authors.forename: B
authors.initials: B
authors.lastname: Sandfeld-Paulsen
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Aggerholm-Pedersen
authors.affiliation: Department of Immunology, Aalborg University Hospital, Denmark.
authors.forename: R
authors.initials: R
authors.lastname: Bæk
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: K R
authors.initials: KR
authors.lastname: Jakobsen
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Meldgaard
authors.affiliation: Department of Pulmonary Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: B H
authors.initials: BH
authors.lastname: Folkersen
authors.affiliation: Department of Pulmonary Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: T R
authors.initials: TR
authors.lastname: Rasmussen
authors.affiliation: Department of Immunology, Aalborg University Hospital, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Varming
authors.affiliation: Department of Immunology, Aalborg University Hospital, Denmark.
authors.forename: M M
authors.initials: MM
authors.lastname: Jørgensen
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: B S
authors.initials: BS
authors.lastname: Sorensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000473:pathology; D055354:Exosomes / Q000473:pathology*; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins
keywords: EV array; Exosomal proteins; Exosomes; NSCLC; Prognostic marker