Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China

Our plain-English summary of Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China, by Z. Jiang, W. Shen, S. Ying, et al (Scientific Reports, 2020).

The study

• Authors: Z. Jiang, W. Shen, S. Ying, Z. Gao, X. He, R. Chen, H. Xia, X. Guo, Y. Fang, Y. Zhang, J. Miao, J. Zhou, X. Zhang, J. Chen, J. Lou
• Journal: Scientific Reports
• Published: 2020;10(1):20373
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Fibulin-3 is an extracellular matrix glycoprotein widely expressed in various tissues. Tissue fibulin-3 expression have never been reported in association with prognosis of mesothelioma. Hence, we sought to determine the association between fibulin-3 expression and mesothelioma survival. We made a tissue microarray, which was comprised of cancer and normal tissue from mesothelioma patients (n = 82) during the period 1998-2017 in China. Fibulin-3 and HGMB1 expression were analyzed by immunohistochemistry method. Kaplan-Meier method and Cox proportional hazard models were used for analyzing survival data. Overall, 61 cases (74.4%) were female; 90.2% were of epithelioid type; the median overall survival time was 12.5 months. Fibulin-3 and HMGB1 were highly expressed in tumor tissue rather than adjacent tissue. The expression of fibulin-3 in tissue was correlated with that of HMGB1 (r = 0.32, P = 0.003). High expression of fibulin-3 in tumor tissue could predict poor survival in patients with mesothelioma (P = 0.02). This remained true in a multivariate model, with a significant hazard ratio of 1.91. We demonstrated that fibulin-3 in tumor tissue was a novel biomarker of poor survival of mesothelioma, suggesting it may be a relevant target for therapeutic intervention.

In plain English

This retrospective study examined stored tumor tissue from 82 mesothelioma patients at four hospitals in China, from 1998 to 2017. Most were women (74.4%) with epithelioid tumors (90.2%), and 62.2% had peritoneal mesothelioma. Asbestos exposure history was investigated for only 27 patients, and 92.6% of them had been exposed at work. The article does not say which asbestos fiber type they were exposed to. The researchers stained the tissue for two proteins, fibulin-3 and HMGB1. Both scored higher in tumor than in nearby non-tumor tissue. Median survival was 12.5 months overall (95% CI 10.5 to 18). The 20 patients with high fibulin-3 had median survival of 9.3 months, against 14 months with low fibulin-3 (P = 0.02). Adjusted for gender, age, subtype, site and treatment, the hazard ratio for high fibulin-3 was 1.91 (95% CI 1.09 to 3.33). HMGB1 was not significantly linked to survival overall, but in pleural mesothelioma, high HMGB1 went with shorter median survival (9.6 vs 13 months). The authors concluded that high tissue fibulin-3 was associated with poor survival. They named small tissue samples and small subgroups as limitations.

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: Retrospective study of archived tumor tissue (tissue microarray with immunohistochemistry staining), with survival analysis using Kaplan-Meier curves and multivariate Cox models
• Who was studied: 82 patients with pathologically diagnosed malignant mesothelioma from four hospitals in China, tissue from 1998 to 2017. 61 (74.4%) were female, mean age 57.5 years, 90.2% epithelioid, 51 (62.2%) peritoneal and 31 (37.8%) pleural. Tumor tissue was available for 82 patients and interpretable adjacent tissue for 67.
• Exposure: The study measured tissue expression of fibulin-3 and HMGB1. Asbestos exposure history was investigated for only 27 patients, and 92.6% of those were occupationally exposed. The article does not identify the fiber type these patients were exposed to; fluoro-edenite is named only in cited research. The title refers to a hand-spinning asbestos exposed area.
• Main results:
  • Tumor tissue showed higher fibulin-3 expression than adjacent tissue (median score 4.0 (3–4) vs 2 (1–2)). HMGB1 was also higher in tumor tissue (7 (3.3–12) vs 4 (1–6)). P less than 0.001 for both.
  • Overall median survival was 12.5 months (95% CI 10.5 to 18); 12 patients (14.6%) were alive at the end of the study.
  • Across all patients, fibulin-3 expression in tissue was correlated with HMGB1 expression (r = 0.32, P = 0.003).
  • 20 patients (24.4%) had high fibulin-3 expression and 41 patients (50%) had high HMGB1 expression.
  • Higher fibulin-3 expression was associated with poorer survival in the Kaplan-Meier analysis (P = 0.02).
  • Median survival was 14 months for patients with low fibulin-3 expression and 9.3 months for those with high expression.
  • In the multivariate Cox model (also including gender, age, subtype, site and treatment), high vs low fibulin-3 expression had a hazard ratio of 1.91 (95% CI 1.09 to 3.33, P = 0.02).
  • In all patients together, HMGB1 expression was not significantly associated with overall survival (HR = 1.22, 95% CI 0.72 to 2.05, P = 0.47). The combination of fibulin-3 and HMGB1 was also not significantly associated (HR = 1.67, 95% CI 0.98 to 2.85, P = 0.06).
  • Among pleural mesothelioma patients, high HMGB1 expression was significantly associated with poorer survival. Median survival was 9.6 months with high vs 13 months with low expression (P = 0.008, Table 3).
  • In subgroup analyses, fibulin-3 expression was significantly associated with survival (P less than 0.05) in patients under 60, women, epithelioid type, peritoneal mesothelioma patients and surgical patients. For example, among patients under 60, median survival was 8 months with high vs 19.5 months with low fibulin-3.
  • Gender, age, subtype, site and treatment were not significantly associated with overall survival in this group of patients.
• The authors' conclusion: The authors concluded that their data showed, for the first time, an association between high fibulin-3 in tumor tissue and poor survival in mesothelioma patients. They suggested tissue fibulin-3 could serve as a prognostic biomarker.
• Limitations the authors state:
  • The study used small tissue samples (tissue microarray cores) that may not represent the whole tumor; the authors used four hospitals to reduce this bias.
  • Sample sizes within each subgroup were small, so the results need confirmation in a larger study.

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: Fibulin-3, Mesothelioma, Glycoprotein, Prognosis, Immunohistochemistry, Epithelioid, Median Overall Survival, High Mobility Group Box 1 (HMGB1).

Related studies

• Hand-spinning chrysotile exposure and risk of malignant mesothelioma: A case-control study in Southeastern China — Z. Jiang, T. Chen, et al. (2018)
• Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population — Z. Jiang, S. Ying, et al. (2017)
• Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases — S. Ying, Z. Jiang, et al. (2017)
• Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis — M.B. Kirschner, E. Pulford, et al. (2015)
• Genome-wide profiling reveals novel microRNAs in hand-spinning-specific chrysotile exposure — J. Jia, X. Guo, et al. (2019)
• HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma — L. Pellegrini, J. Xue, et al. (2017)

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