Glycodelin is a potential novel follow-up biomarker for malignant pleural mesothelioma

Our plain-English summary of Glycodelin is a potential novel follow-up biomarker for malignant pleural mesothelioma, by M.A. Schneider, T. Muley, N.C. Kahn, et al (Oncotarget, 2016).

The study

• Authors: M.A. Schneider, T. Muley, N.C. Kahn, A. Warth, M. Thomas, F.J. Herth, H. Dienemann, M. Meister
• Journal: Oncotarget
• Published: 2016;7(44):71285-71297
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This Heidelberg, Germany study tested whether glycodelin, a pregnancy-related protein, could serve as a marker for malignant pleural mesothelioma (MPM). The authors measured it in stored serum, tumor tissue and pleural-fluid cells. Median serum glycodelin was significantly higher in MPM patients than in patients with non-small cell lung cancer (NSCLC), COPD or pleurisy. Against benign diseases, the area under the curve was 0.857 (95% confidence interval 0.819 to 0.896). Neither glycodelin nor the established marker SMRP alone significantly predicted survival. Patients high in one or both showed borderline significance (P = 0.056). In six patients followed over time, glycodelin was generally lower after first therapy and often rose until death. Glycodelin gene activity was 4.03-fold higher in MPM cells than in benign mesothelial cells. In tumor tissue, strong glycodelin A staining was linked to significantly better survival (P = 0.027). The authors concluded that glycodelin might be a feasible serum marker for diagnosing and monitoring MPM. The article reports no analysis of asbestos exposure. It notes one pleurisy patient with asbestos exposure and the highest glycodelin level who later developed MPM.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Biomarker study using stored biobank serum, tumor tissue, a tissue microarray and pleural effusion cells, with survival analyses
• Who was studied: Patients at the Thoraxklinik, University Hospital Heidelberg, Germany. The groups were: a serum validation cohort of 183 randomly selected MPM patients; a pretherapeutic cohort of 151 untreated patients plus 23 patients with pleurisy; 32 MPM samples and 11 benign mesothelial cell samples for gene expression; and a tissue microarray from 213 patients operated on between 2002 and 2009.
• Exposure: The article reports no analysis of asbestos exposure; it mentions asbestos exposure only for one pleurisy patient. The factor measured was glycodelin (gene PAEP) and its form glycodelin A, in serum and tissue, with SMRP measured for comparison.
• Main results:
  • In the validation cohort, median serum glycodelin in MPM patients was significantly higher than in patients with NSCLC (P < 0.0001), COPD (P < 0.0001) or pleurisy (P = 0.029).
  • Serum glycodelin separated MPM from benign diseases with an area under the curve (AUC) of 0.857 (95% CI 0.819 to 0.896).
  • When NSCLC samples were also included, the AUC fell to 0.75 (95% CI 0.704 to 0.797).
  • In the multivariate analysis of overall survival, age and pathological stage were significant factors. Glycodelin was only weakly significant (P = 0.074), and SMRP was not significant (P = 0.340).
  • Neither serum glycodelin nor SMRP alone was a significant factor for overall survival in the pretherapeutic cohort.
  • Patients with a high serum level of one or both markers showed borderline significance for overall survival (P = 0.056) compared with patients with low levels. In further analyses this was mainly attributable to the epithelial type (P = 0.037).
  • In follow-up samples from six patients with epithelial MPM, glycodelin before therapy was generally higher than after first therapy. It frequently rose during follow-up until the patients died of the tumor.
  • Glycodelin gene (PAEP) expression was 4.03-fold higher in MPM cells (n = 32) than in benign mesothelial cells from pleural effusions (n = 11), P = 0.029.
  • Glycodelin protein was found in all 12 randomly selected MPM tumor samples tested by Western blot.
  • In the tissue microarray, strong glycodelin A staining was linked to significantly better overall survival (P = 0.027). Total glycodelin staining was not a significant prognostic marker (P = 0.131).
  • In the pleurisy group, the patient with the highest serum glycodelin, a never smoker with chronic pleurisy after asbestos exposure, later developed MPM. This is a single case.
• The authors' conclusion: The authors concluded that glycodelin might be a feasible serum marker for diagnosing MPM and for monitoring tumor response to treatment during follow-up.
• Limitations the authors state:
  • Some pleurisy patients had raised glycodelin, but part of these patients were not followed up at the study hospital, so their disease progression could not be clarified.
  • Glycodelin is also expressed by NSCLC, which lowered sensitivity and specificity when MPM and NSCLC were analysed together against benign diseases.
  • Several MPM patients in the validation cohort had low serum glycodelin.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Mesothelial Cells, Pleura, Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Osteopontin, Fibulin-3.

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