Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma

Our plain-English summary of Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma, by C. Tabata, T. Terada, R. Tabata, et al (Journal of Clinical Gastroenterology, 2013).

The study

• Authors: C. Tabata, T. Terada, R. Tabata, S. Yamada, R. Eguchi, Y. Fujimori, T. Nakano
• Journal: Journal of Clinical Gastroenterology
• Published: 2013;47(1):e7-11
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intraperitoneal chemotherapy. Therefore, diagnosing DMPM early is very important. Reactive oxygen species play an important role in asbestos toxicity, which is associated with the pathogenesis of DMPM growth. Thioredoxin-1 (TRX) is a small redox-active protein that demonstrates antioxidative activity associated with tumor growth. Here, we investigated the serum levels of TRX in patients with DMPM and compared them with those of a population that had been exposed to asbestos but did not have DMPM.

Study: The serum concentrations of TRX were measured in 15 DMPM patients and 34 individuals with benign asbestos-related diseases.

Results: We demonstrated that the patients with DMPM had significantly higher serum levels of TRX than the population that had been exposed to asbestos but did not have DMPM.

Conclusions: Our data suggest that serum TRX concentration is a useful serum marker for DMPM.

In plain English

This Japanese study measured a blood protein called thioredoxin-1 (TRX) to see whether it could help diagnose diffuse malignant peritoneal mesothelioma (DMPM), a cancer of the abdominal lining. The authors tested blood serum collected at diagnosis from 49 people seen at Hyogo College of Medicine Hospital from 2006 to 2011. Fifteen had DMPM, and 12 of them had a documented history of asbestos exposure. The other 34 were asbestos-exposed people without DMPM: 19 had pleural plaques and/or asbestosis, and 15 had no asbestos-related lesions. Average TRX was 116.2 ng/mL in the DMPM patients and 40.1 ng/mL in the comparison group (P less than 0.001). At a cutoff of 60 ng/mL, the test identified 66.7% of the DMPM patients (sensitivity) and correctly ruled out 85.3% of the others (specificity). TRX levels in DMPM patients did not differ significantly from those of patients with other cancers. The authors concluded that TRX would be a useful serum marker for DMPM. They also said it is not suitable for telling DMPM apart from other cancers and needs further validation at other institutions in a blinded manner.

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: Hospital-based diagnostic marker study comparing serum TRX levels in patients with DMPM against asbestos-exposed people without DMPM, plus a laboratory experiment on mesothelioma and mesothelial cell lines
• Who was studied: 49 individuals seen at the Department of Respiratory Medicine of Hyogo College of Medicine Hospital, Japan, from 2006 to 2011: 15 with DMPM, 19 with pleural plaques and/or asbestosis, and 15 asbestos-exposed people with no asbestos-related lesions. Sera from 7 patients with other cancers and 5 healthy volunteers never exposed to asbestos were also collected.
• Exposure: Documented history of asbestos exposure: 12 of the 15 DMPM patients and all 34 non-DMPM subjects. Fiber types, products and jobs were not described.
• Main results:
  • In the DMPM patients, mean serum TRX was 116.2 plus or minus 76.9 ng/mL, significantly higher than in the non-DMPM comparison group
  • The comparison group (benign asbestos-related disease patients and asbestos-exposed healthy individuals) had a mean TRX of 40.1 plus or minus 20.4 ng/mL; P less than 0.001 for the comparison with DMPM
  • In distinguishing the 15 DMPM patients from the 34 asbestos-exposed non-DMPM subjects, the area under the ROC curve was 0.790 (95% CI, 0.663-0.918). At a cutoff of 60 ng/mL, sensitivity was 66.7% and specificity was 85.3%.
  • At that cutoff, the positive predictive value was 68.8% and the negative predictive value was 87.9%
  • Among DMPM patients, TRX levels did not differ significantly by asbestos exposure history, and differences by histologic type, age, sex and performance status were not statistically significant
  • TRX levels did not differ significantly between the subjects with benign asbestos-related diseases (40.1 plus or minus 18.7 ng/mL) and the asbestos-exposed healthy subjects (40.0 plus or minus 23.1 ng/mL)
  • TRX levels in DMPM patients did not differ significantly from those in patients with other cancers (99.8 plus or minus 31.7 ng/mL)
  • In the laboratory, the mesothelioma cell lines H28 and H2052 produced significantly more TRX (25.3 plus or minus 6.3 and 20.6 plus or minus 3.3 pg/mL) than the other cell lines, including the mesothelial cell line MeT-5A (5.1 plus or minus 0.7 pg/mL)
• The authors' conclusion: The authors concluded that serum TRX would be a useful serum marker for DMPM, and that high TRX levels support a DMPM diagnosis among asbestos-exposed individuals
• Limitations the authors state:
  • The marker is not ready for clinical use and needs further evaluation and validation in other cohorts from other institutions in a blinded manner
  • TRX is not suitable for distinguishing DMPM from other cancers
  • The test's sensitivity (66.7%) and positive predictive value (68.8%) were not high

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Cytoreductive Surgery, Chemotherapy, Reactive Oxygen Species (ROS).

Related studies

• Is serum thioredoxin-1 a useful clinical marker for malignant pleural mesothelioma? — R. Maeda, C. Tabata, et al. (2011)
• Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma — C. Tabata, S. Kanemura, et al. (2013)
• Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma — C. Tabata, E. Shibata, et al. (2013)
• Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial — B. Trabert, L. Pinto, et al. (2014)
• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma — D.B. Chapel, A.N. Husain, et al. (2017)

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