Wan Lin, Chen Xiaochun, Deng Jun, Zhang Shiliang, Tu Fan, Pei Hao, Hu Renjing, Liu Jun, Yu Hao
Department of Laboratory Medicine, Wuxi Second People's Hospital, Wuxi214000, China.
Department of Laboratory Medicine, Taizhou Second People's Hospital, Taizhou 225300, China.
J Cancer. 2021 Jan 5;12(5):1538-1547. doi: 10.7150/jca.52320. eCollection 2021.
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). 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. 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%, < 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. Plasma exosome-derived BTG-1 may be a potential biomarker for the prognosis in patients with NSCLC.
在本研究中,我们旨在探究血浆外泌体来源的B细胞易位基因1(BTG-1)水平作为非小细胞肺癌(NSCLC)患者预后的预测标志物。通过免疫组织化学(IHC)和逆转录聚合酶链反应(RT-PCR)检测了98例入组患者NSCLC组织及癌旁组织中BTG-1蛋白和BTG-1 mRNA的表达。从262例NSCLC患者的血浆中分离出富含外泌体的组分。采用酶联免疫吸附测定(ELISA)检测血浆外泌体来源的BTG-1水平,以评估其对NSCLC患者预后的预测价值。免疫组织化学染色显示,BTG-1蛋白在NSCLC组织中的阳性表达率为58.16%,而在癌旁组织中为91.84%。RT-PCR显示,NSCLC组织中BTG-1 mRNA表达显著低于癌旁组织(52.04%对87.76%,<0.05)。此外,血浆外泌体来源的BTG-1水平低与肿瘤直径、分期、转移、肿瘤分化程度及癌胚抗原(CEA)水平异常有关。多因素Cox回归分析显示,与血浆外泌体来源的BTG-1水平高的患者相比,血浆外泌体来源的BTG-1水平低的患者无病生存期(DFS)和总生存期(OS)均较短。血浆外泌体来源的BTG-1对3年DFS和3年OS的受试者工作特征曲线下面积(AUROC)分别为0.94(95%可信区间:0.91 - 0.98)和0.94(95%可信区间:0.90 - 0.98)。对于3年DFS,血浆外泌体来源的BTG-1对3年DFS的敏感性为91.0%,特异性为82.3%,对3年OS的敏感性为81.7%,特异性为93.0%。血浆外泌体来源的BTG-1可能是NSCLC患者预后的潜在生物标志物。