Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in patients with suspected pleural mesothelioma

Our plain-English summary of Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in patients with suspected pleural mesothelioma, by T. Sato, Y. Suzuki, T. Mori, et al (Cancer Medicine, 2014).

The study

• Authors: T. Sato, Y. Suzuki, T. Mori, M. Maeda, M. Abe, O. Hino, K. Takahashi
• Journal: Cancer Medicine
• Published: 2014;3(5):1377-84
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma is an aggressive tumor, commonly caused by exposure to asbestos. The prognosis of mesothelioma remains disappointing despite multimodal treatment. We reported previously that N-ERC/mesothelin could be a useful biomarker for the early diagnosis of pleural mesothelioma and developed an enzyme-linked immunosorbent assay (ELISA) system for its detection. However, the reproducibility of our previous 7-16 ELISA system has been revealed to be unsatisfactory. To measure N-ERC/mesothelin more precisely, we developed a new 7-20 ELISA system. The subjects of this study were patients who were referred to our department with suspected pleural mesothelioma. The current study demonstrated that the newly established 7-20 ELISA system improved the sensitivity and specificity for diagnosing pleural mesothelioma compared with the previous system. Moreover, the 7-20 ELISA system showed better reproducibility and displayed the tendency of both higher sensitivity and higher specificity in plasma than in serum. Particularly for the epithelioid type, the area under the curve (AUC) and the diagnostic accuracy of N-ERC/mesothelin were excellent; the AUC was 0.91, the sensitivity was 0.95, and the specificity was 0.76 in plasma. In conclusion, assessment of N-ERC/mesothelin with our newly established 7-20 ELISA system is clinically useful for the precise diagnosis of pleural mesothelioma.

© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

In plain English

This Japanese study tested a new laboratory blood test (the 7–20 ELISA) for N-ERC/mesothelin, a protein the authors had studied as a possible marker of pleural mesothelioma. It compared the new test with the authors' earlier version (the 7–16 ELISA). From June 2005 to March 2013 they prospectively enrolled 53 patients referred with suspected pleural mesothelioma, mainly because of pleural effusion, pleural thickening and a history of asbestos exposure. Of these, 28 had confirmed mesothelioma (21 epithelioid, 5 sarcomatoid, 2 biphasic). The other 25 formed the non-mesothelioma comparison group, including 5 whose condition remained undiagnosed. In repeat-measurement checks, the new test's results varied less than the old test's. Comparing all mesothelioma patients with the comparison group, the area under the curve (a measure of how well a test separates two groups) in plasma was 0.82 with the new test and 0.74 with the old. For epithelioid mesothelioma in plasma, the new test had a sensitivity of 0.95 and a specificity of 0.76. The authors concluded the new test is clinically useful. They also noted that, with so few patients, there may be no significant difference between the two tests.

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: Prospective diagnostic accuracy study comparing a new blood test (7–20 ELISA) with an earlier one (7–16 ELISA), including laboratory validation of the new test
• Who was studied: 53 patients referred to the Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Japan, with suspected pleural mesothelioma, enrolled June 2005 to March 2013. 28 had confirmed pleural mesothelioma (21 epithelioid, 5 sarcomatoid, 2 biphasic). The other 25 were classified as non-mesothelioma patients: 11 lung cancer, 2 other cancers, 7 benign pleuritis and 5 undiagnosed.
• Exposure: The study evaluated a blood test, not an exposure. A history of asbestos exposure was one of the main reasons patients were suspected of having pleural mesothelioma. No fiber types, jobs or doses are reported. N-ERC/mesothelin was measured in serum and plasma with both ELISA systems.
• Main results:
  • Within a single plate, the new 7–20 test's results varied by 0.8% (high), 0.5% (middle) and 1.7% (low) on the three quality-control samples. The old 7–16 test varied by 18.5% (high), 2.4% (middle) and 5.9% (low).
  • Across different plates, the new 7–20 test's results varied by 9.6% (high), 15.1% (middle) and 7.0% (low). The old 7–16 test varied by 18.7%, 22.0% and 12.3%.
  • Results from the two tests correlated closely in the 53 patients (R-squared 0.959 in serum, 0.975 in plasma).
  • With the 7–20 test, N-ERC/mesothelin levels in both serum and plasma were significantly higher in epithelioid mesothelioma than in sarcomatoid and biphasic types, and than in non-mesothelioma patients.
  • All 28 mesothelioma patients versus 25 non-mesothelioma patients: area under the curve was 0.77 (serum) and 0.82 (plasma) with the 7–20 test, and 0.74 (serum) and 0.74 (plasma) with the 7–16 test.
  • 21 epithelioid patients versus 25 non-mesothelioma patients: area under the curve was 0.89 (serum) and 0.91 (plasma) with the 7–20 test, and 0.85 (serum) and 0.86 (plasma) with the 7–16 test.
  • All mesothelioma patients versus others, best sensitivity and specificity: 0.68 and 0.68 in serum (cut-off 6.66 ng/mL) and 0.79 and 0.76 in plasma (4.98 ng/mL) with the 7–20 test. With the 7–16 test: 0.64 and 0.72 in serum (8.14 ng/mL) and 0.71 and 0.72 in plasma (6.14 ng/mL).
  • Epithelioid type versus others, best sensitivity and specificity in plasma: 0.95 and 0.76 (cut-off 4.97 ng/mL) with the 7–20 test, versus 0.81 and 0.76 (7.62 ng/mL) with the 7–16 test. In serum: 0.81 and 0.80 (9.16 ng/mL) with the 7–20 test, versus 0.76 and 0.76 (9.46 ng/mL) with the 7–16 test.
• The authors' conclusion: The authors concluded that measuring N-ERC/mesothelin with their new 7–20 ELISA is clinically useful because of the system's technological improvement. They recommended testing plasma rather than serum.
• Limitations the authors state:
  • The number of patients was small, so there may be no significant difference in any of the comparative measures between the 7–20 and 7–16 tests.
  • Patients came from a single department. The authors said a multicenter clinical trial is needed.
  • Specificity seemed slightly lower than in the authors' previous report. They attributed this to the smaller sample and different subject characteristics.
  • Other markers (SMRP, fibulin-3) were not measured in the same samples.
  • There were not enough data on testing pleural effusion fluid with this ELISA.

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: Mesothelin, Pleural Mesothelioma, Prognosis, Mesothelioma, Biomarker, Epithelioid.

Related studies

• Establishment of a novel specific ELISA system for rat N- and C-ERC/mesothelin. Rat ERC/mesothelin in the body fluids of mice bearing mesothelioma — Y. Hagiwara, Y. Hamada, et al. (2008)
• Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum — J. Creaney, S. Sneddon, et al. (2013)
• Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma — L. Santarelli, S. Staffolani, et al. (2015)
• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)
• Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma — K. Shiomi, Y. Hagiwara, et al. (2008)
• Evaluation of soluble mesothelin-related peptide as a diagnostic marker of malignant pleural mesothelioma effusions: its contribution to cytology — P.A. Canessa, M.C. Franceschini, et al. (2013)

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