Exosomal proteins as prognostic biomarkers in non-small cell lung cancer

B Sandfeld-Paulsen, N Aggerholm-Pedersen, R Bæk, K R Jakobsen, P Meldgaard, B H Folkersen, T R Rasmussen, K Varming, Malene Jørgensen, B S Sorensen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

194 Citationer (Scopus)

Abstract

BACKGROUND: 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.

METHODS: 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).

RESULTS: 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.

CONCLUSION: 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.

OriginalsprogEngelsk
TidsskriftMolecular Oncology
Vol/bind10
Udgave nummer10
Sider (fra-til)1595-1602
Antal sider8
ISSN1574-7891
DOI
StatusUdgivet - 2016

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