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 transmission electron microscopy, 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 compared to the healthy group. Alpha‐2‐HS‐glycoprotein showed diagnostic values with a maximum area under the receiver operating characteristic curve (AUC) as 0.736 for NSCLC vs healthy individuals (P < .0001) and 0.682 for early stage NSCLC vs healthy individuals (P < .01). Extracellular matrix protein 1 showed the diagnostic capacity with AUC values of 0.683 (P < .001) and 0.656 (P < .05) in cancer and early stage NSCLC 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 carcinoembryonic antigen 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.

Uridine‐cytidine kinase 2 (UCK2): A potential diagnostic and prognostic biomarker for lung cancer

“…In addition, up to 40% of TNM classified early stage lung cancer recurred after surgical resection . Thus, developing effective biomarkers for early diagnosis and prognosis of lung cancer are urgently needed …”

Tumor-derived exosomal miR-155-5p and miR-658 in serum as diagnostic biomarkers for early-stage non-small cell lung cancer

“…In addition, western immunoblotting con rmed the two well-known protein markers, including CD63 and TSG101 [19,22], which were enriched in exosomes but absent in cell extracts ( Figure 1C). Besides, GM130 as a negative control was only detected in the cell extracts but not in exosomes [20]. These data demonstrated that the vesicles isolated from serum by ultracentrifugation were truly exosomes.…”

“…Serum biomarkers for diagnosis of NSCLC patients have been widely studied and applied in clinical, such as CEA, CA125, NSE, CYFRA21-1, and CA153 [19,20]. However, there is no any effective biomarker for diagnosis of early-stage NSCLC patients.…”

“…Serum exosomes were isolated using ultracentrifugation according to the procedures as described previously [20,23]. Brie y, the serum was thawed on ice and centrifuged at 10, 000×g for 30 min at 4°C to remove the cellular debris.…”

“…Given that miRNAs are related to the origination and progression of different diseases such as cancers [10], and are dysregulated in several categories of cancer patients. So exosomal miRNAs can be used as molecular biomarkers for cancer diagnosis [19,20]. For instance, plasma exosomal miR-141-3p and miR-375 were signi cantly over-expressed in rectal cancer patients with synchronous liver metastasis, and can be employed as diagnostic markers of rectal cancer aggressiveness and systemic dissemination [21].…”