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P2.01-034 The Pregnancy Associated Endometrial Protein Glycodelin as a Biomarker for Malignant Pleural Mesothelioma
January 2017
dose-limiting factor in chest radiotherapy. However, the radiative dosage is not effective for most of patients because of avoiding RILT. Therefore, novel diagnosis methods reveal individual potential RILT are required. For now, increasing evidence illustrates that exosomes in circulating fluids provide a promising way as biomarkers for noninvasive disease diagnosis. Exosomes are 30e150 nm particles which are released from cells into the extracellular environment and thousands of proteins have been identified in plasma exosomes. Whether exosomal proteomics analysis could benefit lung cancer patients with appropriate radiative dosage and prevent RILT remains to be studied. Methods: Plasma samples were collected from RILT patients with grade I and II, and no RILT individuals matched with age, gender and blood collection time after 10 to 30Gy radiation within 6 months. Plasma exosomes were accessed by 110,000g ultracentrifugation and visualized by NS300 equipment. The raw data of exosomal proteomics profiles of RILT patients and no-RILT individuals were generated by LC-MS and its expression were verified by western blot. Results: In the present study, we revealed 17 exosomal protein participated in wounding response and two of them were correlated with RILT clinic stage. A2M (Alpha-2-macroglobulin) was decreased in RILT patients and FGB (Fibrinogen beta chain) was increased in RILT patients. Furthermore, A2M was decreasing from no radiative damage patients to that of RILT grade I to II, and the FGB expression in exosomes showed positive correlation with RILT from low to high level. The patients with low FGB expression in plasma exosomes could tolerate higher radiative dosage until the FGB was upregulated in plasma. Conclusion: LC-MS is an efficient method for exosomal proteomics analysis and we reveal two stable targets A2M and FGB, which could indicate the potential of patients suffering RILT after radiotherapy. The two novel targets could serve as promising diagnosis biomarkers for avoiding RILT. Keywords: radiation-induced lung toxicity, Exosomal proteomics
P2.01-034 The Pregnancy Associated Endometrial Protein Glycodelin as a Biomarker for Malignant Pleural Mesothelioma Topic: Proteins in Lung Cancer and Proteomics Marc Schneider,1 Arne Warth,2 Thomas Muley,1 Michael Thomas,3 Felix Jf Herth,3 Hendrik Dienemann,4 Michael Meister1 1Translational
Abstracts
S805
Research Unit (Stf), Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Thoraxklinik at Heidelberg University Hospital, Heidelberg/Germany, 2Institute of Pathology, Heidelberg University Hospital, Heidelberg/ Germany, 3Department of Thoracic Oncology, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Thoraxklinik at Heidelberg University Hospital, Heidelberg/Germany, 4Department of Thoracic Surgery, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Thoraxklinik at Heidelberg University Hospital, Heidelberg/Germany Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a short survival time arising from the mesothelial cells of the pleura. MPM is mainly associated with asbestos exposure and a strong inflammatory reaction. The common treatment of MPM combines macroscopic complete resection and adjuvant or neoadjuvant chemotherapy, respectively. Soluble mesothelin and osteopontin are current available biomarker for malignant mesothelioma with moderate sensitivity and specificity. Glycodelin is an immune system modulator well described during pregnancy. It is involved in invasion of the trophoblast and in regulation of the immunotolerance between the maternal immune system and the fetus. Methods: With a commercial ELISA, we measured the glycodelin serum concentrations of patients with MPM. In addition, we analyzed the glycodelin gene expression using quantitative PCR and stained glycodelin in formalin-fixed paraffin embedded tissue slides. Results: We found high glycodelin concentrations in the serum of patients with MPM compared to benign lung diseases. Patients with high glycodelin serum concentrations exhibited a worse overall survival. Moreover, glycodelin serum levels correlated with tumor response to treatment. A comparison of soluble mesothelinrelated proteins (SMRP) and glycodelin in the serum of a large patient cohort demonstrated that the detection of both soluble factors can increase the reliable diagnostic of MPM. Glycodelin mRNA and protein was highly expressed in MPM tumors compared to normal lung tissue. Conclusion: In this study, we first described the expression of glycodelin in MPM. Altogether, glycodelin seems to be a new potential serum biomarker for the aggressive malignant pleural mesothelioma. Keywords: malignant pleural mesothelioma, biomarker, Glycodelin
dose-limiting factor in chest radiotherapy. However, the radiative dosage is not effective for most of patients because of avoiding RILT. Therefore, novel diagnosis methods reveal individual potential RILT are required. For now, increasing evidence illustrates that exosomes in circulating fluids provide a promising way as biomarkers for noninvasive disease diagnosis. Exosomes are 30e150 nm particles which are released from cells into the extracellular environment and thousands of proteins have been identified in plasma exosomes. Whether exosomal proteomics analysis could benefit lung cancer patients with appropriate radiative dosage and prevent RILT remains to be studied. Methods: Plasma samples were collected from RILT patients with grade I and II, and no RILT individuals matched with age, gender and blood collection time after 10 to 30Gy radiation within 6 months. Plasma exosomes were accessed by 110,000g ultracentrifugation and visualized by NS300 equipment. The raw data of exosomal proteomics profiles of RILT patients and no-RILT individuals were generated by LC-MS and its expression were verified by western blot. Results: In the present study, we revealed 17 exosomal protein participated in wounding response and two of them were correlated with RILT clinic stage. A2M (Alpha-2-macroglobulin) was decreased in RILT patients and FGB (Fibrinogen beta chain) was increased in RILT patients. Furthermore, A2M was decreasing from no radiative damage patients to that of RILT grade I to II, and the FGB expression in exosomes showed positive correlation with RILT from low to high level. The patients with low FGB expression in plasma exosomes could tolerate higher radiative dosage until the FGB was upregulated in plasma. Conclusion: LC-MS is an efficient method for exosomal proteomics analysis and we reveal two stable targets A2M and FGB, which could indicate the potential of patients suffering RILT after radiotherapy. The two novel targets could serve as promising diagnosis biomarkers for avoiding RILT. Keywords: radiation-induced lung toxicity, Exosomal proteomics
P2.01-034 The Pregnancy Associated Endometrial Protein Glycodelin as a Biomarker for Malignant Pleural Mesothelioma Topic: Proteins in Lung Cancer and Proteomics Marc Schneider,1 Arne Warth,2 Thomas Muley,1 Michael Thomas,3 Felix Jf Herth,3 Hendrik Dienemann,4 Michael Meister1 1Translational
Abstracts
S805
Research Unit (Stf), Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Thoraxklinik at Heidelberg University Hospital, Heidelberg/Germany, 2Institute of Pathology, Heidelberg University Hospital, Heidelberg/ Germany, 3Department of Thoracic Oncology, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Thoraxklinik at Heidelberg University Hospital, Heidelberg/Germany, 4Department of Thoracic Surgery, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Thoraxklinik at Heidelberg University Hospital, Heidelberg/Germany Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a short survival time arising from the mesothelial cells of the pleura. MPM is mainly associated with asbestos exposure and a strong inflammatory reaction. The common treatment of MPM combines macroscopic complete resection and adjuvant or neoadjuvant chemotherapy, respectively. Soluble mesothelin and osteopontin are current available biomarker for malignant mesothelioma with moderate sensitivity and specificity. Glycodelin is an immune system modulator well described during pregnancy. It is involved in invasion of the trophoblast and in regulation of the immunotolerance between the maternal immune system and the fetus. Methods: With a commercial ELISA, we measured the glycodelin serum concentrations of patients with MPM. In addition, we analyzed the glycodelin gene expression using quantitative PCR and stained glycodelin in formalin-fixed paraffin embedded tissue slides. Results: We found high glycodelin concentrations in the serum of patients with MPM compared to benign lung diseases. Patients with high glycodelin serum concentrations exhibited a worse overall survival. Moreover, glycodelin serum levels correlated with tumor response to treatment. A comparison of soluble mesothelinrelated proteins (SMRP) and glycodelin in the serum of a large patient cohort demonstrated that the detection of both soluble factors can increase the reliable diagnostic of MPM. Glycodelin mRNA and protein was highly expressed in MPM tumors compared to normal lung tissue. Conclusion: In this study, we first described the expression of glycodelin in MPM. Altogether, glycodelin seems to be a new potential serum biomarker for the aggressive malignant pleural mesothelioma. Keywords: malignant pleural mesothelioma, biomarker, Glycodelin