Role of Prosaposin and Extracellular Sulfatase Sulf-1 Detection in Pleural Effusions as Diagnostic Biomarkers of Malignant Mesothelioma

Our plain-English summary of Role of Prosaposin and Extracellular Sulfatase Sulf-1 Detection in Pleural Effusions as Diagnostic Biomarkers of Malignant Mesothelioma, by L. Zallocco, R. Silvestri, F. Ciregia, et al (Biomedicines, 2022).

The study

• Authors: L. Zallocco, R. Silvestri, F. Ciregia, A. Bonotti, R. Marino, R. Foddis, A. Lucacchini, L. Giusti, M.R. Mazzoni
• Journal: Biomedicines
• Published: 2022;10(11)
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma is an aggressive malignancy with poor prognosis. Unilateral pleural effusion is frequently the initial clinical sign requiring therapeutic thoracentesis, which also offers a diagnostic opportunity. Detection of soluble biomarkers can support diagnosis, but few show good diagnostic accuracy. Here, we studied the expression levels and discriminative power of two putative biomarkers, prosaposin and extracellular sulfatase SULF-1, identified by proteomic and transcriptomic analysis, respectively. Pleural effusions from a total of 44 patients (23 with mesothelioma, 8 with lung cancer, and 13 with non-malignant disease) were analyzed for prosaposin and SULF-1 by enzyme-linked immunosorbent assay. Pleural effusions from mesothelioma patients had significantly higher levels of prosaposin and SULF-1 than those from non-malignant disease patients. Receiver-operating characteristic (ROC) analysis showed that both biomarkers have good discriminating power as pointed out by an AUC value of 0.853 (p = 0.0005) and 0.898 (p < 0.0001) for prosaposin and SULF-1, respectively. Combining data ensued a model predicting improvement of the diagnostic performance (AUC = 0.916, p < 0.0001). In contrast, prosaposin couldn’t discriminate mesothelioma patients from lung cancer patients while ROC analysis of SULF-1 data produced an AUC value of 0.821 (p = 0.0077) but with low sensitivity. In conclusion, prosaposin and SULF-1 levels determined in pleural effusion may be promising biomarkers for differential diagnosis between mesothelioma and non-malignant pleural disease. Instead, more patients need to be enrolled before granting the possible usefulness of these soluble proteins in differentiating mesothelioma pleural effusions from those linked to lung cancer.

In plain English

This study measured two proteins, prosaposin and extracellular sulfatase SULF-1, in pleural fluid (fluid around the lung) to see whether they could help diagnose malignant pleural mesothelioma. The fluid came from 44 patients at the University-Hospital of Pisa, Italy, collected from 2004 to 2008. Of these, 23 had mesothelioma (all epithelioid subtype), 8 had lung adenocarcinoma and 13 had benign pleural disease. Prosaposin was significantly higher in mesothelioma fluid than in benign disease fluid, but did not differ significantly from lung adenocarcinoma fluid. SULF-1 was significantly higher in mesothelioma fluid than in both other groups. The study used a measure called AUC (area under the curve) to judge how well each protein told the groups apart. For telling mesothelioma from benign disease, the AUC was 0.853 (95% confidence interval 0.724 to 0.981) for prosaposin and 0.898 (0.797 to 0.999) for SULF-1. A model combining both predicted an AUC of 0.916 (0.823 to 1.000). For telling mesothelioma from lung adenocarcinoma, SULF-1 had an AUC of 0.821 (0.658 to 0.984), with 100% specificity but 56.50% sensitivity. The authors concluded that the proteins may be added to other supporting tests when invasive procedures are not feasible, but that larger studies are needed. They noted the small groups.

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 biomarker study. The authors measured two proteins by ELISA in prospectively collected pleural effusion samples. They also ran a separate analysis of a public cancer gene-expression database (UALCAN, using TCGA data).
• Who was studied: Pleural effusions from 44 patients collected by thoracentesis at the University-Hospital of Pisa, Italy, from 2004 to 2008. The patients were 23 with malignant pleural mesothelioma (all epithelioid subtype), 8 with lung adenocarcinoma and 13 with benign pleural disease. All samples were taken before any treatment.
• Exposure: The study did not examine asbestos exposure as a variable. It measured levels of two proteins (prosaposin and SULF-1) in pleural fluid. Table 1 lists asbestos exposure as 5 in the mesothelioma group and 'not available' for the other two groups. No fiber types are reported.
• Main results:
  • Prosaposin was significantly higher in mesothelioma fluid (1773 plus or minus 214.4 ng/mL, mean plus or minus SEM) than in benign pleural disease fluid (706 plus or minus 112.4 ng/mL), p = 0.0003.
  • In lung adenocarcinoma fluid, prosaposin was 1254 plus or minus 266.7 ng/mL. This was lower than in mesothelioma and higher than in benign disease, but neither difference was statistically significant.
  • SULF-1 was significantly higher in mesothelioma fluid (0.178 ng/mL) than in benign disease fluid (0.069 ng/mL, p less than 0.0001) and lung adenocarcinoma fluid (0.089 ng/mL, p = 0.0062).
  • Prosaposin, mesothelioma versus benign disease: AUC 0.853 (95% CI 0.724 to 0.981, p = 0.0005), with 76.90% specificity and 87% sensitivity at a cut-off of 813.2 ng/mL.
  • SULF-1, mesothelioma versus benign disease: AUC 0.898 (95% CI 0.797 to 0.999, p less than 0.0001), with 92.30% specificity and 73.90% sensitivity at a cut-off of 0.12 ng/mL.
  • For mesothelioma versus benign disease, a logistic-regression model combining both proteins predicted an AUC of 0.916 (95% CI 0.823 to 1.000, p less than 0.0001), with 84.60% specificity and 91.30% sensitivity.
  • SULF-1, mesothelioma versus lung adenocarcinoma: AUC 0.821 (95% CI 0.658 to 0.984, p = 0.0077), with 100% specificity and 56.50% sensitivity.
  • In the database (TCGA) analysis, prosaposin gene activity was significantly higher in epithelioid mesothelioma than in biphasic mesothelioma (p = 0.006).
  • In the database (TCGA) analysis, SULF-1 gene activity was significantly higher in mesothelioma with normal (wild-type) TP53 than in tumors with mutated TP53 (p = 0.002). Low or medium SULF-1 levels were associated with reduced survival, but this difference was not statistically significant (p = 0.07).
• The authors' conclusion: The authors concluded that measuring prosaposin and SULF-1 in pleural fluid may be added to other supporting tests for diagnosing mesothelioma when invasive procedures are not feasible. They added that larger studies of patients and controls are needed to establish a definitive diagnostic role.
• Limitations the authors state:
  • Only a small number of pleural fluid samples was examined for each patient group.
  • Mesothelioma patients were not selected by positive or negative cytology, so possible overestimation of diagnostic accuracy cannot be ruled out.
  • All mesotheliomas were of the epithelioid subtype, which limits usefulness for other subtypes.
  • The small number of lung adenocarcinoma patients does not allow a precise judgement on whether the proteins can separate mesothelioma from lung adenocarcinoma.
  • The TCGA database held only enough mesothelioma samples to compare the epithelioid and biphasic subtypes.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Biomarker, Mesothelioma, Pleural Mesothelioma, Prognosis, Thoracentesis, Lung Cancer, Differential Diagnosis.

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