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Detection of TGF-β in pleural effusions for diagnosis and prognostic stratification of malignant pleural mesothelioma.
Lung Cancer ( IF 5.3 ) Pub Date : 2019-11-18 , DOI: 10.1016/j.lungcan.2019.11.013
Paul Stockhammer 1 , Till Ploenes 2 , Dirk Theegarten 3 , Martin Schuler 4 , Sandra Maier 5 , Clemens Aigner 6 , Balazs Hegedus 2
Affiliation  

OBJECTIVES Malignant pleural mesothelioma (MPM) is an aggressive malignancy with dismal prognosis but variable course of disease. To support diagnosis and to risk stratify patients, more reliable biomarkers are warranted. Emerging evidence underlines a functional role of transforming growth factor-beta (TGF-β) in MPM tumorigenesis though its utility as a clinical biomarker remains unexplored. MATERIALS AND METHODS Corresponding pleural effusions and serum samples taken at primary diagnosis were analyzed for TGF-β by ELISA, and for mesothelin (SMRP) by chemiluminescence enzyme immunoassay. Tumor load was quantified in MPM patients by volumetric analysis of chest CT scans. All findings were correlated with clinicopathological characteristics. RESULTS In total 48 MPM patients, 24 patients with non-malignant pleural disease (NMPD) and 30 patients with stage IV lung cancer were enrolled in this study. Pleural effusions from MPM patients had significantly higher TGF-β levels than from NMPD or lung cancer patients (p < 0.0001; AUC for MPM vs NMPD: 0.78, p = 0.0001). Both epithelioid and non-epithelioid MPM were associated with higher TGF-β levels (epithelioid: p < 0.05; non-epithelioid: p < 0.0001) and levels of TGF-β correlated with disease stage (p = 0.003) and with tumor volume (p = 0.002). Interestingly, high TGF-β levels in pleural effusion, but not in serum, was significantly associated with inferior overall survival (TGF-beta ≥14.36 ng/mL: HR 3.45, p = 0.0001). This correlation was confirmed by multivariate analysis. In contrast, effusion SMRP levels were exclusively high in epithelioid MPM, negatively correlated with effusion TGF-β levels and did not provide prognostic information. CONCLUSION TGF-β levels determined in pleural effusion may be a promising biomarker for diagnosis and prognostic stratification of MPM.

中文翻译:

胸腔积液中TGF-β的检测对恶性胸膜间皮瘤的诊断和预后分层。

目的恶性胸膜间皮瘤(MPM)是一种侵袭性的恶性肿瘤,预后不良,病程可变。为了支持诊断并对患者进行分层风险,需要使用更可靠的生物标志物。新兴证据强调了转化生长因子-β(TGF-β)在MPM肿瘤发生中的功能性作用,尽管其作为临床生物标记物的效用尚待探索。材料与方法ELISA法分析初次诊断时相应的胸腔积液和血清样本的TGF-β,化学发光酶免疫法分析其间皮素(SMRP)。通过对胸部CT扫描进行体积分析,对MPM患者的肿瘤负荷进行了量化。所有发现均与临床病理特征相关。结果共有48位MPM患者,本研究招募了24例非恶性胸膜疾病(NMPD)患者和30例IV期肺癌患者。MPM患者的胸腔积液的TGF-β水平明显高于NMPD或肺癌患者(p <0.0001; MPM与NMPD的AUC:0.78,p = 0.0001)。上皮和非上皮类MPM均与较高的TGF-β水平相关(上皮类:p <0.05;非上皮类:p <0.0001),并且TGF-β的水平与疾病阶段(p = 0.003)和肿瘤体积相关( p = 0.002)。有趣的是,胸腔积液中高水平的TGF-β而不是血清中的高TGF-β显着与总生存期差有关(TGF-β≥14.36ng / mL:HR 3.45,p = 0.0001)。通过多变量分析证实了这种相关性。相比之下,上皮样MPM中的积液SMRP水平很高,与积液TGF-β水平呈负相关,且未提供预后信息。结论胸腔积液测定的TGF-β水平可能是MPM诊断和预后分层的有前途的生物标志物。
更新日期:2019-11-18
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