Performance of biomarkers SMRP, CA125, and CYFRA 21-1 as potential tumor markers for malignant mesothelioma and lung cancer in a cohort of workers formerly exposed to asbestos

Our plain-English summary of Performance of biomarkers SMRP, CA125, and CYFRA 21-1 as potential tumor markers for malignant mesothelioma and lung cancer in a cohort of workers formerly exposed to asbestos, by M. Gube, D. Taeger, D.G. Weber, et al (Archives of Toxicology, 2011).

The study

• Authors: M. Gube, D. Taeger, D.G. Weber, B. Pesch, P. Brand, G. Johnen, A. Müller-Lux, I.M. Gross, T. Wiethege, A. Weber, H.J. Raithel, T. Kraus, T. Brüning
• Journal: Archives of Toxicology
• Published: 2011;85(3):185-92
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of the study is to examine the cancer-predictive values of SMRP (soluble mesothelin-related peptides), CA125, and CYFRA21-1 as potential tumor markers for lung cancer and malignant mesothelioma in a cohort of workers formerly exposed to asbestos. A voluntary surveillance program has been established for German workers with former asbestos exposure. A subgroup of 626 subjects with a mean age of 63 years (range 53-70 years) at baseline was enrolled in an extended health examination program with high-resolution computer tomography (HRCT) of the chest and blood drawing between 1993 and 1997. Serum concentrations of SMRP, CA125, and CYFRA21-1 were measured in archived serum samples in 2005 and 2006. A mortality follow-up was conducted through 2007. So far, 12 cases with lung cancer and 20 cases with malignant mesothelioma have been observed in this cohort. The average time between sample collection and diagnosis was 4.7 years. Analyzed biomarkers showed low sensitivities (5-25%) and positive predictive values (4-30%) for both cancer sites. Marker combinations resulted in sensitivities between 5 and 50% and positive predictive values ranging from 3 to 14%. Even in those cases, where biomarker concentrations were available within 36 months before diagnosis, no trend for increasing biomarker levels was observed. The analyzed tumor markers were characterized by high specificities, but low sensitivities. SMRP, CA125, and CYFRA21-1 alone or in combination were less suitable to serve as predictors for the diagnosis of lung cancer or malignant mesothelioma. However, a prospective study with annual sampling might reveal a better predictive value of these markers.

In plain English

This German study tested stored blood from 626 former asbestos workers who had chest scans and blood draws in a surveillance program from 1993 to 1997. The authors measured three proposed tumor markers (SMRP, CA125, CYFRA 21-1) and followed the group to 2007. Twenty developed malignant mesothelioma and twelve lung cancer, on average 4.71 years after blood was drawn. SMRP and CA125 were not significantly higher in either cancer group. CYFRA 21-1 was significantly higher in lung cancer cases (median 1.57 versus 1.08 ng/ml). Alone, SMRP flagged 10.0% and CA125 5.0% of mesothelioma cases, and CYFRA 21-1 none; CYFRA 21-1 flagged 25.0% of lung cancer cases. Combinations flagged at most 15.0% of mesothelioma and 50.0% of lung cancer cases; at most 4.1% of positive results were mesothelioma cases and at most 14.3% lung cancer cases. Levels showed no clear rise before diagnosis. The authors concluded performance was poor, possibly because samples were taken long before diagnosis. They listed frozen storage as a limitation but cited their earlier finding that storage did not affect SMRP or CYFRA 21-1, though it raised CA125.

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: Cohort study (a surveillance cohort) in which stored serum samples were analyzed retrospectively for tumor markers, with follow-up for cancer
• Who was studied: 626 workers formerly exposed to asbestos (575 male, 92%) who took part at least once in an extended annual surveillance program with high-resolution CT of the chest at six study centers in Germany, 1993 to 1997. Ages ranged from 53 to 70 years at enrollment, with a median of 63 in those without cancer and 65 in cancer cases. Follow-up ran to April 30, 2007.
• Exposure: Former occupational asbestos exposure, with fiber types not specified. Exposure was assessed as fiber years. Median duration of exposure was 25 years in lung cancer cases, 14 years in mesothelioma cases and 19 years in the others. Serum markers were measured against these cut-offs: SMRP 1.5 nmol/L, CA125 34 KIU/l, CYFRA 21-1 3.3 ng/ml.
• Main results:
  • During follow-up to 2007, 20 cases of malignant mesothelioma and 12 cases of lung cancer were identified among the 626 workers.
  • The average (mean) time between blood sampling and diagnosis was 4.71 years, with a range of 1 to 13 years.
  • Median SMRP was 0.90 nmol/L in lung cancer cases, 0.84 nmol/L in mesothelioma cases and 0.71 nmol/L in workers without these cancers. The differences were not statistically significant.
  • Median CA125 was 10.80 KIU/l in mesothelioma cases, 11.80 KIU/l in lung cancer cases and 10.40 KIU/l in workers without these cancers. The differences were not significant.
  • Median CYFRA 21-1 was 1.57 ng/ml in lung cancer cases, compared with 1.08 ng/ml in workers without these cancers. This difference was significant (P = 0.0062). The median in mesothelioma cases was 1.12 ng/ml.
  • For mesothelioma, SMRP had a sensitivity of 10.0%, a specificity of 91.8% and a positive predictive value of 3.9%.
  • For lung cancer, SMRP had a sensitivity of 16.7% and a specificity of 91.9%.
  • For mesothelioma, CA125 had a sensitivity of 5.0%, a specificity of 95.9% and a positive predictive value of 3.9%.
  • For lung cancer, CA125 had a sensitivity of 16.7%, a specificity of 96.1% and a positive predictive value of 7.7%.
  • For lung cancer, CYFRA 21-1 had a sensitivity of 25.0%, a specificity of 98.9% and a positive predictive value of 30.0%.
  • CYFRA 21-1 was above its cut-off in none of the mesothelioma cases, so its sensitivity and positive predictive value for mesothelioma could not be calculated. Its specificity for mesothelioma was 98.4%.
  • For mesothelioma, combinations of the markers had sensitivities of 5.0 to 15.0%, specificities of 87.0 to 94.4% and positive predictive values of 2.9 to 4.1%.
  • For lung cancer, the SMRP plus CA125 combination had a sensitivity of 25%. The other combinations had sensitivities of 41.7 to 50.0%.
  • For lung cancer, the positive predictive values of the marker combinations ranged from 4.1 to 14.3%.
  • For mesothelioma, the areas under the ROC curve were 0.55 for SMRP, 0.50 for CA125 and 0.52 for CYFRA 21-1. The authors described this as very poor performance.
  • For lung cancer, the area under the ROC curve was 0.64 for SMRP (P = 0.0772) and 0.73 for CYFRA 21-1 (P = 0.0015).
  • Over time, marker values in the cancer cases did not show a clear trend toward diagnosis. A gradual increase was seen in only a few cases.
• The authors' conclusion: The authors concluded that the cancer-predictive values of SMRP, CA125, CYFRA 21-1 and their combinations were poor for both mesothelioma and lung cancer. They suggested this might be explained by the relatively long time between sample collection and diagnosis. They called for future studies with repeated sampling at intervals of 1 year or less.
• Limitations the authors state:
  • The serum samples had been stored frozen for several years, which could have affected marker concentrations. The authors cited their own earlier work finding that SMRP and CYFRA 21-1 were not affected by long-term storage, whereas CA125 showed increased values.

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: Biomarker, Soluble Mesothelin-Related Peptides (SMRP), Tumor Marker, Malignant Mesothelioma, Lung Cancer, Asbestos Exposure, High-Resolution CT (HRCT).

Related studies

• Soluble mesothelin-related peptides (SMRP) - high stability of a potential tumor marker for mesothelioma — D.G. Weber, D. Taeger, et al. (2007)
• Assessment of Confounding Factors Affecting the Tumor Markers SMRP, CA125, and CYFRA21-1 in Serum — D.G. Weber, G. Johnen, et al. (2010)
• Cancer mortality in a surveillance cohort of German males formerly exposed to asbestos — B. Pesch, D. Taeger, et al. (2010)
• Diagnostic value of mesothelin in pleural fluids: comparison with CYFRA 21-1 and CEA — R. Filiberti, S. Parodi, et al. (2013)
• Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis — D.G. Weber, S. Casjens, et al. (2014)
• Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions — G. Salama, M. Miédougé, et al. (1998)

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