Palstrøm Nicolai B, Overgaard Martin, Licht Peter, Beck Hans C
Department of Clinical Biochemistry, Odense University Hospital, 5000 Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.
Cancers (Basel). 2023 Jan 19;15(3):641. doi: 10.3390/cancers15030641.
Malignant pleural mesothelioma (MPM) is an asbestos-associated, highly aggressive cancer characterized by late-stage diagnosis and poor prognosis. Gold standards for diagnosis are pleural biopsy and cytology of pleural effusion (PE), both of which are limited by low sensitivity and markedly inter-observer variations. Therefore, the assessment of PE biomarkers is considered a viable and objective diagnostic tool for MPM diagnosis. We applied a novel affinity-enrichment mass spectrometry-based proteomics method for explorative analysis of pleural effusions from a prospective cohort of 84 patients referred for thoracoscopy due to clinical suspicion of MPM. Protein biomarkers with a high capability to discriminate MPM from non-MPM patients were identified, and a Random Forest algorithm was applied for building classification models. Immunohistology of pleural biopsies confirmed MPM in 40 patients and ruled out MPM in 44 patients. Proteomic analysis of pleural effusions identified panels of proteins with excellent diagnostic properties (90-100% sensitivities, 89-98% specificities, and AUC 0.97-0.99) depending on the specific protein combination. Diagnostic proteins associated with cancer growth included galactin-3 binding protein, testican-2, haptoglobin, Beta ig-h3, and protein AMBP. Moreover, we also confirmed previously reported diagnostic accuracies of the MPM markers fibulin-3 and mesothelin measured by two complementary mass spectrometry-based methods. In conclusion, a novel affinity-enrichment mass spectrometry-based proteomics identified panels of proteins in pleural effusion with extraordinary diagnostic accuracies, which are described here for the first time as biomarkers for MPM.
恶性胸膜间皮瘤（MPM）是一种与石棉相关的高度侵袭性癌症，其特征为晚期诊断和预后不良。诊断的金标准是胸膜活检和胸腔积液（PE）细胞学检查，这两种方法都受到低敏感性和明显的观察者间差异的限制。因此，评估PE生物标志物被认为是MPM诊断的一种可行且客观的诊断工具。我们应用了一种基于亲和富集质谱的新型蛋白质组学方法，对因临床怀疑MPM而接受胸腔镜检查的84例患者的前瞻性队列中的胸腔积液进行探索性分析。确定了具有高度区分MPM患者和非MPM患者能力的蛋白质生物标志物，并应用随机森林算法构建分类模型。胸膜活检的免疫组织学检查证实40例患者患有MPM，44例患者排除MPM。胸腔积液的蛋白质组学分析确定了具有优异诊断特性（敏感性90 - 100%，特异性89 - 98%，AUC 0.97 - 0.99）的蛋白质组，具体取决于特定的蛋白质组合。与癌症生长相关的诊断蛋白包括半乳糖凝集素-3结合蛋白、睾丸蛋白聚糖-2、触珠蛋白、βig-h3和蛋白质AMBP。此外，我们还通过两种基于质谱的互补方法证实了先前报道的MPM标志物纤维连接蛋白-3和间皮素的诊断准确性。总之，一种基于亲和富集质谱的新型蛋白质组学方法在胸腔积液中鉴定出了具有非凡诊断准确性的蛋白质组，本文首次将其描述为MPM的生物标志物。
