Fibulin-3 as a biomarker of response to treatment in malignant mesothelioma

Our plain-English summary of Fibulin-3 as a biomarker of response to treatment in malignant mesothelioma, by V. Kovac, M. Dodic-Fikfak, N. Arneric, et al (Radiology and Oncology, 2015).

The study

• Authors: V. Kovac, M. Dodic-Fikfak, N. Arneric, V. Dolzan, A. Franko
• Journal: Radiology and Oncology
• Published: 2015;49(3):279-85
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Fibulin-3 is a new potential biomarker for malignant mesothelioma (MM). This study evaluated the potential applicability of fibulin-3 plasma levels as a biomarker of response to treatment and its prognostic value for progressive disease within 18 months. The potential applicability of fibulin-3 in comparison with or in addition to soluble mesothelin-related peptides (SMRP) was also assessed.

Patients And Methods: The study included 78 MM patients treated at the Institute of Oncology Ljubljana between 2007 and 2011. Fibulin-3 levels in plasma samples obtained before treatment and in various responses to treatment were measured with the enzyme-linked immunosorbent assay.

Results: In patients evaluated before the treatment, fibulin-3 levels were not influenced by histopathological sub-types, tumour stages or the presence of metastatic disease. Significantly higher fibulin-3 levels were found in progressive disease as compared to the levels before treatment (Mann-Whitney [U] test = 472.50, p = 0.003), in complete response to treatment (U = 42.00, p = 0.010), and in stable disease (U = 542.00, p = 0.001). Patients with fibulin-3 levels exceeding 34.25 ng/ml before treatment had more than four times higher probability for developing progressive disease within 18 months (odds ratio [OR] = 4.35, 95% confidence interval [CI] 1.56-12.13). Additionally, patients with fibulin-3 levels above 34.25 ng/ml after treatment with complete response or stable disease had increased odds for progressive disease within 18 months (OR = 6.94, 95% CI 0.99-48.55 and OR = 4.39, 95% CI 1.63-11.81, respectively).

Conclusions: Our findings suggest that in addition to SMRP fibulin-3 could also be helpful in detecting the progression of MM.

In plain English

This panel study followed 78 malignant mesothelioma patients (70 pleural, 8 peritoneal) treated at the Institute of Oncology Ljubljana, Slovenia, between 2007 and 2011. Asbestos exposure was confirmed in 67 (85.9%). The authors measured plasma fibulin-3, a proposed mesothelioma marker, before treatment and at different responses to treatment. Pre-treatment levels did not differ significantly by tumour subtype, stage or spread. Levels were significantly higher in progressive disease than before treatment, in complete response, or in stable disease. Pre-treatment levels above 34.25 ng/ml were linked to higher odds of progressive disease within 18 months (OR 4.35, 95% CI 1.56–12.13). After treatment, levels above that cut-off gave odds ratios of 6.94 (95% CI 0.99–48.55, p = 0.051) in complete response and 4.39 (95% CI 1.63–11.81) in stable disease. In distinguishing progressive disease from other responses, a second marker, SMRP, had a larger area under the ROC curve (84.2%, 95% CI 76.8–91.7) than fibulin-3 (68.3%, 95% CI 57.9–78.7). The authors concluded fibulin-3 could help detect progression but was not proven useful for evaluating treatment response. They noted wide confidence intervals from small numbers.

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: Panel study (longitudinal, each patient as own control) measuring a blood biomarker at different disease and treatment phases
• Who was studied: 78 patients with biopsy-proven malignant mesothelioma (57 male, 21 female; 70 pleural, 8 peritoneal) treated at the Institute of Oncology Ljubljana, Slovenia, between March 2007 and June 2011; 135 blood samples in total
• Exposure: The study measured plasma fibulin-3 levels and compared them with SMRP. Asbestos exposure was assessed semi-quantitatively. It was confirmed in 67 patients (low 24, medium 21, high 22) and not proven with certainty in 11. No fiber types were named. Patients were treated with cisplatin plus low-dose gemcitabine or pemetrexed, with surgery in some.
• Main results:
  • Among 33 patients evaluated before treatment, fibulin-3 levels did not differ significantly between histopathological subtypes or tumour stages, nor by metastatic disease (U = 73.00, p = 0.854)
  • There was no significant difference between fibulin-3 levels before treatment and levels in complete response, partial response or stable disease
  • Fibulin-3 levels were significantly higher in progressive disease than before treatment (U = 472.50, p = 0.006)
  • Fibulin-3 levels were significantly higher in progressive disease than in complete response (U = 42.00, p = 0.020) or stable disease (U = 542.00, p = 0.002)
  • In ROC analysis comparing progressive disease with complete response, partial response or stable disease, the area under the curve for fibulin-3 was 68.3% (95% CI 57.9–78.7, p = 0.002)
  • The fibulin-3 cut-off of 34.25 ng/ml had a sensitivity of 82.2%
  • The fibulin-3 cut-off of 34.25 ng/ml had a specificity of 47.7%
  • In the same ROC comparison, the area under the curve for SMRP (mesothelin) was 84.2% (95% CI 76.8–91.7, p less than 0.001)
  • Patients with pre-treatment fibulin-3 above 34.25 ng/ml had higher odds of progressive disease within 18 months (OR = 4.35, 95% CI 1.56–12.13, p = 0.005)
  • For fibulin-3 above 34.25 ng/ml after treatment, the odds of progressive disease within 18 months were OR = 6.94 (95% CI 0.99–48.55, p = 0.051) in complete response and OR = 4.39 (95% CI 1.63–11.81, p = 0.003) in stable disease
  • For pre-treatment SMRP above 1.50 nmol/L, the odds ratio for progressive disease was 5.86 (95% CI 1.68–22.40)
  • When fibulin-3 and SMRP were analysed together, the odds did not change considerably from the single-marker analyses
• The authors' conclusion: The authors concluded that, in addition to SMRP, fibulin-3 could be helpful in detecting the progression of malignant mesothelioma. Unlike SMRP, it has not been proven useful for evaluating tumour response to treatment.
• Limitations the authors state:
  • Confidence intervals were wide because the number of subjects was low
  • A larger sample size is needed to increase study power and validate the results

Topics

Medical terms in this study, explained in our Lexicon: Fibulin-3, Biomarker, Mesothelioma, Soluble Mesothelin-Related Peptides (SMRP), Odds Ratio, confidence interval.

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• Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma — H.I. Pass, S.M. Levin, et al. (2012)
• Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population — Z. Jiang, S. Ying, et al. (2017)
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