Schneider Marc A, Muley Thomas, Kahn Nicolas C, Warth Arne, Thomas Michael, Herth Felix J F, Dienemann Hendrik, Meister Michael
Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Roentgenstraße, Heidelberg, Germany.
Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany.
Oncotarget. 2016 Nov 1;7(44):71285-71297. doi: 10.18632/oncotarget.12474.
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a short survival time arising from the mesothelial cells of the pleura. Soluble mesothelin-related peptide (SMRP), osteopontin or EFEMP1 (Fibulin-3) are well described biomarkers for malignant mesothelioma with moderate sensitivity and specificity. In this study, we characterized the expression of glycodelin, a marker for risk pregnancy, in MPM by RNA and protein analyses and investigated its potential as a MPM biomarker. We were able to detect glycodelin in the serum of MPM patients. Compared to benign lung diseases, the serum levels were significant increased. Patients with high glycodelin serum levels revealed a worse overall survival. The glycodelin serum levels correlated with the tumor response to treatment. A comparison of SMRP and glycodelin serum measurement in a large patient cohort demonstrated that the detection of both soluble factors can increase the reliable diagnostic of MPM. Glycodelin was highly expressed in MPM tumors. Analyses of a tissue micro array indicated that the immunomodulatory form glycodelin A was expressed in MPM and correlated with the survival of the patients. Altogether, glycodelin seems to be a new potential biomarker for the aggressive malignant pleural mesothelioma.
恶性胸膜间皮瘤(MPM)是一种罕见且侵袭性强、生存期短的肿瘤,起源于胸膜间皮细胞。可溶性间皮素相关肽(SMRP)、骨桥蛋白或EFEMP1(纤维连接蛋白-3)是已被充分描述的恶性间皮瘤生物标志物,其敏感性和特异性中等。在本研究中,我们通过RNA和蛋白质分析对妊娠风险标志物糖蛋白1进行了表征,并研究了其作为MPM生物标志物的潜力。我们能够在MPM患者的血清中检测到糖蛋白1。与良性肺部疾病相比,血清水平显著升高。糖蛋白1血清水平高的患者总生存期较差。糖蛋白1血清水平与肿瘤对治疗的反应相关。在一个大型患者队列中对SMRP和糖蛋白1血清检测进行比较表明,检测这两种可溶性因子可提高MPM诊断的可靠性。糖蛋白1在MPM肿瘤中高表达。组织微阵列分析表明,免疫调节形式的糖蛋白1A在MPM中表达,并与患者的生存期相关。总之,糖蛋白1似乎是侵袭性恶性胸膜间皮瘤的一种新的潜在生物标志物。