Serum Calretinin as a Biomarker in Malignant Mesothelioma

Our plain-English summary of Serum Calretinin as a Biomarker in Malignant Mesothelioma, by C. Zupanc, A. Franko, D. Štrbac, et al (Journal of Clinical Medicine, 2021).

The study

• Authors: C. Zupanc, A. Franko, D. Štrbac, M. Dodič Fikfak, V. Kovač, V. Dolžan, K. Goričar
• Journal: Journal of Clinical Medicine
• Published: 2021;10(21)
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The early diagnosis of malignant mesothelioma (MM) could improve the prognosis of MM patients. To confirm an MM diagnosis, an immunohistochemical analysis of several tumor tissue markers, including calretinin, is currently required. Our aim is to evaluate serum calretinin as a potential biomarker in asbestos-related diseases, especially in MM. Our study includes 549 subjects: 164 MM patients, 117 subjects with asbestosis, 195 subjects with pleural plaques and 73 occupationally asbestos-exposed subjects without asbestos-related diseases. The serum calretinin concentration was determined with a commercially available enzyme immunoassay. Data on the soluble mesothelin-related peptides (SMRP) concentration are available from previous studies. MM patients had a significantly higher calretinin concentration than subjects without disease, subjects with pleural plaques or subjects with asbestosis (all p < 0.001). The histological type was significantly associated with serum calretinin: patients with sarcomatoid MM had lower calretinin than patients with the epithelioid type (p = 0.001). In a ROC curve analysis, the area under the curve for calretinin concentration predicting MM was 0.826 (95% CI = 0.782-0.869; p < 0.001). At the cutoff value of 0.32 ng/mL, sensitivity was 0.683, while specificity was 0.886. The combination of calretinin and SMRP had the highest predictive value. Calretinin is a useful biomarker that can distinguish MM from other asbestos-related diseases and could, therefore, contribute to an earlier non-invasive diagnosis of MM.

In plain English

This Slovenian study measured serum calretinin, a blood protein, to see whether it could help distinguish malignant mesothelioma from other asbestos-related conditions. It included 549 people: 164 mesothelioma patients and 385 occupationally asbestos-exposed workers (117 with asbestosis, 195 with pleural plaques, 73 with no asbestos-related disease). Median serum calretinin was 0.52 ng/mL in mesothelioma patients versus 0.12 to 0.18 ng/mL in the other groups, a statistically significant difference. Calretinin distinguished mesothelioma patients from all others with an area under the curve of 0.826 (95% confidence interval 0.782 to 0.869). At a cutoff of 0.32 ng/mL, sensitivity was 0.683 and specificity 0.886. Women had higher levels than men. Sarcomatoid mesothelioma had significantly lower levels than the epithelioid type. Cumulative asbestos exposure was not associated with calretinin levels. In a subset of 416 people, including 68 with mesothelioma, combining calretinin with another marker, SMRP, gave the highest area under the curve, 0.877 (95% confidence interval 0.821 to 0.932). The authors concluded that serum calretinin could serve as a diagnostic marker for mesothelioma. They noted some exposure and SMRP data were missing.

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: Biomarker study comparing serum calretinin levels across groups of patients and asbestos-exposed workers (mesothelioma patients versus other groups), with ROC curve analysis
• Who was studied: 549 subjects in Slovenia. There were 164 malignant mesothelioma (MM) patients treated at the Institute of Oncology Ljubljana between November 2001 and March 2019. The other 385 were occupationally asbestos-exposed workers evaluated in Ljubljana between 1999 and 2003: 117 with asbestosis, 195 with pleural plaques and 73 without asbestos-related disease. Mesothelioma cases were 144 pleural and 20 peritoneal.
• Exposure: Occupational asbestos exposure. Fiber types are not specified in this article. Exposure was measured as cumulative exposure in fibers/cm3 years and categorized as low (under 11), medium (11 to 20) or high (over 20). For some mesothelioma patients, exposure was estimated from work history.
• Main results:
  • Median serum calretinin was:
• 0.52 (0.23 to 1.43) ng/mL in MM patients
• 0.13 (0.08 to 0.2) ng/mL in subjects with asbestosis
• 0.18 (0.12 to 0.25) ng/mL in subjects with pleural plaques
• 0.12 (0.07 to 0.2) ng/mL in subjects without asbestos-related disease

MM patients had significantly higher levels than each other group (all p less than 0.001).

• Comparing MM patients with all other subjects, the area under the curve for calretinin was 0.826 (95% CI 0.782 to 0.869). At a cutoff of 0.32 ng/mL, sensitivity was 0.683 and specificity was 0.886.
• Women had higher calretinin levels than men (p less than 0.001). Among MM patients, women's levels were higher but the difference was not statistically significant (p = 0.315).
• Among MM patients, median calretinin was:
• 0.67 ng/mL in epithelioid MM
• 0.51 ng/mL in biphasic MM
• 0.17 ng/mL in sarcomatoid MM

Sarcomatoid MM was significantly lower than epithelioid MM (p = 0.001).

• Patients with peritoneal MM tended to have higher calretinin than patients with pleural MM: median 1.00 ng/mL versus 0.48 ng/mL. The difference was not statistically significant (p = 0.065).
• Calretinin levels were not significantly associated with MM stage (p = 0.794) or ECOG performance status (p = 0.191).
• Cumulative asbestos exposure was not associated with calretinin levels. In subjects with asbestosis, longer time of exposure was associated with slightly higher calretinin (Spearman's rho = 0.187, p = 0.045).
• In a subset of 416 subjects (68 with MM) with both markers measured:
• calretinin alone: area under the curve 0.847
• SMRP alone: 0.800
• the two combined: 0.877 (95% CI 0.821 to 0.932)

The combination had sensitivity 0.735 and specificity 0.920 at its cutoff score.

• The authors' conclusion: The authors concluded that serum calretinin was elevated in MM patients and could serve as a minimally invasive diagnostic marker differentiating MM from other asbestos-related diseases. They also concluded that combining calretinin with SMRP gave the best predictive value.
• Limitations the authors state:
  • Asbestos exposure and SMRP data were not available for all subjects.
  • Data on the number of asbestos bodies were not available.
  • Calretinin was not measured in healthy people without occupational asbestos exposure.
  • No data on kidney (renal) function were available, and MM patients and other subjects were not age-matched.

Topics

Medical terms in this study, explained in our Lexicon: Calretinin, Biomarker, Malignant Mesothelioma, Prognosis, Pleural Plaques, Soluble Mesothelin-Related Peptides (SMRP), Sarcomatoid, Epithelioid.

Related studies

• The association of genetic factors with serum calretinin levels in asbestos-related diseases — C. Zupanc, A. Franko, et al. (2023)
• Serum Survivin Levels and Outcome of Chemotherapy in Patients with Malignant Mesothelioma — K. Goričar, V. Kovač, et al. (2015)
• Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients — I. Raiko, I. Sander, et al. (2010)
• Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma — D. Štrbac, K. Goričar, et al. (2017)
• Calretinin as a blood-based biomarker for mesothelioma — G. Johnen, K. Gawrych, et al. (2017)
• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma — C. Jiménez-Ramírez, S. Casjens, et al. (2019)

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