Tumor‐derived exosomal proteins as diagnostic biomarkers in non‐small cell lung cancer

Abstract

Accumulating evidence supports a role for exosomal protein in diagnosis. The purpose of this study was to identify the tumor‐derived exosomal biomarkers in the serum that improve the diagnostic value in Chinese non‐small cell lung cancer (NSCLC) patients. Serum exosomes were isolated from healthy donors (n=46) and NSCLC patients (n=125) by ultracentrifugation and were characterized using TEM, qNano and immunoblotting. Proteomic profiles (by mass spectrometry) revealed multiple differentially expressed proteins in the healthy and NSCLC groups. The exosomal expression levels of alpha‐2‐HS‐glycoprotein (AHSG) and extracellular matrix protein 1 (ECM1) increased significantly in the NSCLC patients as compared to the healthy group. AHSG showed diagnostic values with a maximum area under the ROC curve (AUC) as 0.736 for NSCLC vs. healthy individuals (P<0.0001) and 0.682 for early‐stage NSCLC vs. healthy individuals (P<0.01). ECM1 presented the diagnostic capacity with AUC values of 0.683 (P<0.001) and 0.656 (P<0.05) in cancer and early‐stage NSCLC as compared to healthy individuals. When AHSG was combined with ECM1, the AUCs were 0.795 and 0.739 in NSCLC and early‐stage patients, respectively. Taken together, the combination of AHSG, ECM1, and CEA improved the diagnostic potential of NSCLC. The diagnosis values were AUC of 0.938 for NSCLC and 0.911 for early‐stage NSCLC vs. healthy individuals. Our results suggest that novel proteomic signatures found in serum exosomes of NSCLC patients show potential usefulness as diagnostic tools.

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