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

Abstract

BackgroundUse 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.MethodsExosomes 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).ResultsThe 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.ConclusionWe 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.

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

“…Li, Zhang, Zheng, Liu, & Chen, 2017; Pietrowska et al, 2017; Pocsfalvi et al, 2016; Sandfeld-Paulsen, Aggerholm-Pedersen, et al, 2016; Sandfeld-Paulsen, Jakobsen, et al, 2016; Sinha et al, 2018; Tanase et al, 2017; Taylor, Zacharias, & Gercel-Taylor, 2011; van Niel et al, 2018; Weidle et al, 2017)) (Fig. 1).…”

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

“…However, several of the discovered biomarkers either did not quite reflect the clinical disease, or required highly invasive procedures to obtain, and therefore could not be included in routine clinical practice . Additionally, restricted availability of tissue for screening of biomarkers, or those requiring highly invasive procedures for procuring the tissue samples, as found in lung cancer, limits the success of tissue‐based biomarker discovery in cancer . This calls for the need of more accurate and minimally invasive biomarkers for cancer treatment, which makes the biomarkers from liquid biopsies the most coveted in the field .…”

“…1 Additionally, restricted availability of tissue for screening of biomarkers, or those requiring highly invasive procedures for procuring the tissue samples, as found in lung cancer, limits the success of tissue-based biomarker discovery in cancer. 3,4 This calls for the need of more accurate and minimally invasive biomarkers for cancer treatment, which makes the biomarkers from liquid biopsies the most coveted in the field. 5 Blood or urine-based biomarkers are capable of being collected using minimally invasive procedures, and can be sampled all through the disease course or before and after specific treatments, to monitor disease progression.…”

Exosomes as Theranostics for Lung Cancer

“…Profiling the whole proteome of exosomes by mass spectroscopy has revealed various biomarkers in prostate cancer and bladder cancer. A study involving 276 patients with NSCLC identified NY-ESO-1, EGFR, PLAP, EpCAM, and Alix as protein biomarkers for overall survival (Sandfeld-Paulsen, Aggerholm-Pedersen, et al, 2016). Exosomes derived from blood plasma were successfully used for evaluation of multimarker models using the Extracellular Vesicle Array (EV Array) system consisting of 37 antibodies targeting lung cancer-related proteins.…”