Combined serum mesothelin and carcinoembryonic antigen measurement in the diagnosis of malignant mesothelioma

Our plain-English summary of Combined serum mesothelin and carcinoembryonic antigen measurement in the diagnosis of malignant mesothelioma, by K. Fukuoka, K. Kuribayashi, S. Yamada, et al (Molecular and Clinical Oncology, 2013).

The study

• Authors: K. Fukuoka, K. Kuribayashi, S. Yamada, K. Tamura, C. Tabata, T. Nakano
• Journal: Molecular and Clinical Oncology
• Published: 2013;1(6):942-948
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a highly aggressive tumor associated with asbestos exposure. The identification of a marker specific for MM may be of considerable value for the early detection of this tumor and may be used in particular to screen groups with a history of asbestos exposure. The aim of this study was to evaluate serum soluble mesothelin-related peptide (SMRP) levels as a diagnostic marker for MM and investigate whether its diagnostic value is enhanced by combination with other biomarkers. Serum SMRP levels were measured using a quantitative enzyme-linked immunosorbent assay in 96 patients with MM, 55 patients with lung cancer and 39 individuals with a history of asbestos exposure. Receiver operating characteristic curves were constructed for performance evaluation. Stepwise logistic regression analysis was used to select marker combinations (MCs). Serum SMRP levels in patients with MM were significantly higher compared to those in the other groups (P<0.001). The sensitivity of SMRP levels in diagnosing MM was 56% and its specificity for MM vs. lung cancer and individuals with asbestos exposure was 87 and 92%, respectively. The area under the curve (AUC) was 0.76 [95% confidence interval (CI): 0.68-0.83] for the differentiation between MM and lung cancer and 0.78 (95% CI: 0.71-0.86) for the differentiation between MM and individuals with asbestos exposure. For the MC of presence of effusion, SMRP and carcinoembryonic antigen (CEA) levels, the AUC for the differentiation between MM and lung cancer (0.92; 95% CI: 0.88-0.97) and the differentiation between MM and individuals with asbestos exposure (0.93; 95% CI: 0.87-1.0) was significantly higher compared to that for SMRP alone (P=0.0001 and 0.0058, respectively). While the specificity of this MC was comparable to SMRP alone, its sensitivity was ∼20% higher compared to that of SMRP alone. Therefore, combining SMRP and CEA improves the diagnostic performance of SMRP alone. A combination of serum biomarkers, including SMRP, may facilitate the non-invasive diagnosis of MM.

In plain English

This retrospective, single-center Japanese study tested whether the blood marker soluble mesothelin-related peptide (SMRP) helped diagnose malignant mesothelioma. It included 96 patients with mesothelioma (91 pleural, 5 peritoneal), 55 with lung cancer and 39 asbestos-exposed people. SMRP levels were significantly higher in mesothelioma patients than in the other groups. At a 1.5 nM cut-off, SMRP detected 56% (95% confidence interval: 46-66%) of mesothelioma patients. It correctly tested negative in 87% (95% CI: 76-95%) of lung cancer patients and 92% (95% CI: 79-98%) of asbestos-exposed individuals. The authors combined SMRP with another marker, carcinoembryonic antigen (CEA), and with whether fluid had collected in the chest or abdomen. This combination detected 76% (95% CI: 64-85%) of mesothelioma patients and correctly tested negative in 88% (95% CI: 74-96%) and 90% (95% CI: 68-99%) of the same two groups, and scored significantly higher than SMRP alone on an accuracy measure. The authors concluded that combining SMRP and CEA improved on SMRP alone. They noted the results may be optimistic because the same data were used to build and test the combination.

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 diagnostic accuracy study of serum biomarkers at a single center (Hyogo College of Medicine, Japan)
• Who was studied: 190 adults (age 20 or older): 96 patients with pathologically proven malignant mesothelioma (91 pleural, 5 peritoneal; 74 of the 91 pleural cases were stage IV), 55 patients with lung cancer, and 39 individuals with a history of asbestos exposure. Among the asbestos-exposed group, 16 had pleural plaque, 7 benign asbestos pleurisy, 3 asbestosis, 5 asbestosis plus benign asbestos pleurisy, 2 round atelectasis and 6 no imaging abnormalities. Study dates are not given.
• Exposure: The study measured blood markers (SMRP, CYFRA and CEA), not asbestos doses. Asbestos exposure history was used to define one comparison group: individuals with asbestos exposure proven by history or medically, of whom 26 were occupational and 13 environmental. Among mesothelioma patients, 55 had occupational, 27 environmental and 14 no asbestos exposure. No fiber types are named.
• Main results:
  • Serum SMRP levels were significantly higher in mesothelioma patients (median 1.88 nM) than in lung cancer patients (median 0.65 nM) and asbestos-exposed individuals (median 0.64 nM); P<0.001.
  • At a 1.5 nM cut-off, SMRP sensitivity for mesothelioma was 56% (95% CI: 46-66%). Specificity was 87% (95% CI: 76-95%) versus lung cancer and 92% (95% CI: 79-98%) versus asbestos-exposed individuals.
  • CYFRA had sensitivity of 63% for mesothelioma and specificity of 49% versus lung cancer. Sensitivity did not differ significantly from SMRP (P=0.157). SMRP's specificity versus lung cancer was significantly higher than CYFRA's (P<0.001).
  • For SMRP alone, the area under the curve (AUC) was 0.76 (95% CI: 0.68-0.83) for telling mesothelioma from lung cancer and 0.78 (95% CI: 0.71-0.86) for telling mesothelioma from asbestos-exposed individuals.
  • SMRP levels were significantly higher in epithelioid mesothelioma (median 2.47 nM) than in sarcomatoid mesothelioma (median 0.8 nM); P=0.04. There was no significant association between SMRP levels and pleural mesothelioma stage.
  • The marker combination (presence of effusion, SMRP and CEA) had sensitivity of 76% (95% CI: 64-85%) for mesothelioma. Specificity was 88% (95% CI: 74-96%) versus lung cancer and 90% (95% CI: 68-99%) versus asbestos-exposed individuals.
  • The combination's AUC was 0.92 (95% CI: 0.88-0.97) for mesothelioma versus lung cancer, significantly higher than SMRP alone (P=0.0001).
  • The combination's AUC was 0.93 (95% CI: 0.87-1.0) for mesothelioma versus asbestos-exposed individuals, significantly higher than SMRP alone (P=0.0058).
  • Three of the five pleural mesothelioma patients with stage I-II disease were above the combination's cut-off. None of them had elevated SMRP alone.
• The authors' conclusion: The authors concluded that combining SMRP and CEA improved the diagnostic performance of SMRP alone, and that a combination of serum biomarkers including SMRP may facilitate non-invasive diagnosis and early detection of pleural mesothelioma.
• Limitations the authors state:
  • The same data were used both to select the marker combination and to assess its performance, so the evaluation may have been optimistic.
  • Data came from a single center; the authors recommend validation in a multicenter study.
  • Prospective research is still needed to confirm whether such a biomarker combination is useful for diagnosing early-stage pleural mesothelioma.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Carcinoembryonic Antigen (CEA), Malignant Mesothelioma, Asbestos Exposure, Soluble Mesothelin-Related Peptides (SMRP), Biomarker, Lung Cancer, confidence interval.

Related studies

• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions — G. Salama, M. Miédougé, et al. (1998)
• Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma — A. Yasumitsu, C. Tabata, et al. (2010)
• Combined CA125 and mesothelin levels for the diagnosis of malignant mesothelioma — J. Creaney, I. van Bruggen, et al. (2007)
• Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma — L. Santarelli, S. Staffolani, et al. (2015)
• Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment — B.D. Grigoriu, A. Scherpereel, et al. (2007)

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