Plasma exosome-derived B-cell translation gene 1: a predictive marker for the prognosis in patients with non-small cell lung cancer

J Cancer. 2021 Jan 5;12(5):1538-1547. doi: 10.7150/jca.52320. eCollection 2021.

Abstract

Objective: In this study, we wanted to investigate the plasma exosome-derived B-cell translocation gene 1 (BTG-1) level as a predictive marker for the prognosis in patients with Non-small cell lung cancer (NSCLC). Patients and Methods: The expression of BTG-1 protein and BTG-1 mRNA in NSCLC tissues and adjacent tissues of 98 enrolled patients were detected by immunohistochemistry (IHC), and RT-PCR. Exosome-rich fractions were isolated from the plasma of 262 NSCLC patients. ELISA was used to detect plasma exosome-derived BTG-1 levels to evaluate the predictive value for the prognosis in patients with NSCLC. Results: IHC staining showed that the positive expression rate of BTG-1 protein in NSCLC tissues was 58.16%, whereas that in adjacent tissues was 91.84%. RT-PCR showed that BTG-1 mRNA expression was significantly lower in NSCLC tissues than in adjacent tissues (52.04% vs 87.76%, P < 0.05). Moreover, low plasma exosome-derived BTG-1 levels were related to tumor diameter, stage, metastasis, the degree of tumor differentiation, and abnormal carcinoembryonic antigen (CEA) levels. Multivariate Cox regression analysis showed that both the disease-free survival (DFS) and overall survival (OS) were shorter in patients with low plasma exosome-derived BTG-1 level compared with patients with high plasma exosome-derived BTG-1 level. The AUROC of plasma exosome-derived BTG-1 for 3-year DFS and 3-year OS were 0.94(95% CI; 0.91-0.98) and 0.94(95% CI: 0.90-0.98), respectively. For 3-year DFS, plasma exosome-derived BTG-1 had a sensitivity 91.0% and a specificity 82.3% for 3-year DFS, and a sensitivity 81.7% and a specificity 93.0% for 3-year OS, respectively. Conclusions: Plasma exosome-derived BTG-1 may be a potential biomarker for the prognosis in patients with NSCLC.

Keywords: B-cell translocation gene 1; biomarker; exosomal; non-small cell lung cancer; prognosis.