Diagnostic and prognostic value of soluble syndecan-1 in pleural malignancies

Our plain-English summary of Diagnostic and prognostic value of soluble syndecan-1 in pleural malignancies, by F. Mundt, G. Heidari-Hamedani, G. Nilsonne, et al (BioMed Research International, 2014).

The study

• Authors: F. Mundt, G. Heidari-Hamedani, G. Nilsonne, M. Metintas, A. Hjerpe, K. Dobra
• Journal: BioMed Research International
• Published: 2014;2014:419853
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The distinction between malignant and benign pleural effusions is a diagnostic challenge today and measuring soluble biomarkers could add to the diagnostic accuracy. Syndecan-1 is a proteoglycan involved in various cellular functions and is cleaved from the cell surface in a regulated manner. The shed fragment, which can be recovered in effusion supernatant and in serum, retains its binding capacities, but often with different functions and signalling properties than the cell-bound form.

Aim: This study aimed to investigate the diagnostic and prognostic value of soluble syndecan-1 in pleural effusions and sera from patients with pleural malignancies.

Study Design: Using two cohorts of patients, we assessed the diagnostic and prognostic value of soluble syndecan-1 in pleural effusions and sera, using enzyme-linked immunosorbent assays.

Results: In pleural effusions, syndecan-1 distinguished malignant and benign diseases, with an odds ratio of 8.59 (95% CI 3.67 to 20.09). Furthermore, syndecan-1 in pleural effusions predicted a survival difference for patients with pleural metastatic disease and malignant mesothelioma of 11.2 and 9.2 months, respectively. However, no such effects were seen when syndecan-1 was measured in serum.

Conclusion: Soluble syndecan-1 is a promising candidate biomarker for the cytopathological diagnosis and prognostication of malignant pleural effusions.

In plain English

This study tested soluble syndecan-1, a protein shed from cell surfaces, as a marker in fluid around the lungs (pleural effusions) and in blood serum. The authors measured it in 256 effusions from Huddinge, Sweden, collected 2005 to 2011 (74 carcinoma, 89 malignant mesothelioma, 93 benign) and in 231 serum samples from Eskisehir, Turkey, collected 2002 to 2004. In effusions, syndecan-1 was higher in malignant than in benign cases and predicted malignancy with an odds ratio of 8.59 (95% CI 3.67 to 20.09). Serum levels did not separate the groups. Among patients with pleural metastases, median survival was 12.9 months with lower effusion levels and 1.7 months with higher levels. Among mesothelioma patients it was 17.0 versus 7.8 months. A serum survival difference in mesothelioma (9.0 versus 11.0 months, 19 patients with survival data) was not statistically significant. The paper did not report asbestos-exposure measurements or analyze exposure-related disease risk. The authors concluded that effusion syndecan-1 separates malignant from benign conditions. They noted it is not enough on its own to diagnose an individual case, and that high levels may merely reflect tumour burden.

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: Diagnostic and prognostic biomarker study using two prospectively and consecutively collected patient cohorts (pleural effusions and sera), with syndecan-1 measured by ELISA and compared with osteopontin
• Who was studied: 256 pleural effusions (74 carcinoma, 89 malignant mesothelioma, 93 benign) from Karolinska University Hospital, Huddinge, Sweden, 2005 to 2011. 231 serum samples (74 carcinoma, 91 malignant mesothelioma, 66 benign conditions, including 24 benign asbestos pleuritis) from Eskisehir Osmangazi University, Turkey, 2002 to 2004. A separate set of 18 effusions was collected in 2012 to 2013.
• Exposure: The paper did not report asbestos-exposure measurements or analyze exposure-related disease risk. The factor studied was the level of soluble syndecan-1 (and osteopontin) in effusion fluid and serum. In a table note, the authors attributed the high proportion of women among the Turkish mesothelioma serum patients 'most likely' to environmental asbestos and erionite exposure.
• Main results:
  • Syndecan-1 was significantly higher in malignant than in benign pleural effusions. Neither syndecan-1 nor osteopontin differentiated patient groups in serum.
  • In pleural effusions, syndecan-1 predicted malignant disease with an odds ratio of 8.59 (95% CI 3.67 to 20.09).
  • In pleural effusions, the area under the ROC curve was 0.71 (95% CI 0.65, 0.78). At a cutoff of 65.7 ng/mL, sensitivity was 74.9% and specificity 61.3%.
  • In serum, syndecan-1 predicted malignant disease poorly (odds ratio 1.31, 95% CI 0.26 to 6.65; AUC 0.51).
  • Osteopontin in effusions also predicted malignant disease, with an odds ratio of 1.39 (95% CI 1.03, 1.88) and an AUC of 0.65.
  • Patients with pleural metastases: median survival was 12.9 months with effusion syndecan-1 below 235.1 ng/mL and 1.7 months with higher levels (hazard ratio 2.38, 95% CI 1.56 to 5.44).
  • Malignant mesothelioma patients: with an effusion syndecan-1 cutoff of 100.2 ng/mL, median survival was 17.0 months in the 'low' group and 7.8 months in the 'high' group (hazard ratio 2.77, 95% CI 1.35 to 5.68).
  • Mesothelioma patients with serum syndecan-1 above the median (144 ng/mL) had a median survival of 9.0 months, versus 11.0 months for those below it. This difference was not statistically significant (hazard ratio 1.43, 95% CI 0.63 to 3.98).
  • In 18 paired effusion samples, the authors reported a positive correlation between syndecan-1 staining on tumour cells and soluble syndecan-1 levels (r = 0.36, P = 0.14).
• The authors' conclusion: The authors concluded that syndecan-1 measured in pleural effusion fluid separates malignant from benign conditions and is linked to patient survival. They suggested measuring it could be a valuable clinical tool, alone or in a panel of soluble biomarkers.
• Limitations the authors state:
  • Disease stage was not available for the mesothelioma patients. VEGF was measured in 16 effusions as a substitute marker for stage.
  • Survival data for the serum cohort were available for only 19 patients, too few to set hazard-ratio-based cutoffs, so the median was used instead.
  • The link between higher soluble syndecan-1 and shorter survival might simply reflect tumour burden.
  • The marker's discriminatory power is insufficient for use as the only diagnostic marker in an individual patient.
  • The lung and breast adenocarcinoma subgroups were too small to show statistical significance for the survival trend.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Biomarker, Odds Ratio, Malignant Mesothelioma.

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• The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor — K. Hollevoet, K. Nackaerts, et al. (2012)
• Use of cholesterol and soluble tumour markers CEA and syndecan-2 in pleural effusions in cases of inconclusive cytology — M. Gulyas, J. Fillinger, et al. (2019)
• Effect of syndecan-1 overexpression on mesenchymal tumour cell proliferation with focus on different functional domains — F. Zong, E. Fthenou, et al. (2010)
• Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin — G. Ak, Y. Tada, et al. (2017)

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