Comparison between plasma and serum osteopontin levels: usefulness in diagnosis of epithelial malignant pleural mesothelioma

Our plain-English summary of Comparison between plasma and serum osteopontin levels: usefulness in diagnosis of epithelial malignant pleural mesothelioma, by A. Cristaudo, R. Foddis, A. Bonotti, et al (The International Journal of Biological Markers, 2010).

The study

• Authors: A. Cristaudo, R. Foddis, A. Bonotti, S. Simonini, A. Vivaldi, G. Guglielmi, N. Ambrosino, P.A. Canessa, A. Chella, M. Lucchi, A. Mussi, L. Mutti
• Journal: The International Journal of Biological Markers
• Published: 2010;25(3):164-70
• Cited by: 41 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: A potential role of serum osteopontin (OPN) and serum mesothelin-related peptide (SMRP) in the diagnosis of malignant pleural mesothelioma (MPM) has been recently reported. Although the most important data regarding the role of OPN in MPMs derive from the marker's measurement in serum samples, most commercial laboratory kits for OPN assay are suitable only for measuring plasma levels, as indicated by the manufacturers. Our study aimed to evaluate the influence of preanalytic variables on serum and plasma OPN, to compare serum and plasma OPN in the same population, and to assess whether OPN levels can aid in the diagnostic distinction of patients with MPM versus benign respiratory disease (BRD) and healthy subjects exposed to asbestos.

Methods: The influence of preanalytic variables such as the length of storage at different temperatures and the number of thawings of samples on serum and plasma OPN measurements were evaluated. We measured OPN in 239 plasma samples from 207 asbestos-exposed subjects including 94 healthy controls and 113 subjects with BRD, and 32 patients with epithelial MPM, employing a commercially available ELISA. Serum OPN was measured in 196 of the same 239 samples from 80 healthy subjects, 92 BRD patients and 24 MPM patients.

Results: We found that both serum and plasma OPN levels were influenced by storage at -80°C and by the number of thawings, while serum OPN was influenced also by storage at room temperature. Plasma and serum OPN levels were significantly higher (p<0.0001) in patients with epithelial MPM than in the healthy control group and the BRD group. The application of a ROC curve for plasma OPN resulted in an AUC value of 0.780 with a best cutoff of 878.65 ng/mL, with a sensitivity of 68.8% and a specificity of 84.5%. The AUC for sOPN was 0.725 with a best cutoff of 16.06 ng/mL, with a sensitivity of 62.5% and a specificity of 87.3%. Within the control group no significant correlation was observed between age, duration of asbestos exposure, pack-years in current smokers, lung function or imaging parameters and plasma or serum OPN.

Conclusions: These data suggest that plasma OPN and serum OPN are not influenced by confounding factors such as age, smoking habits and asbestos exposure. Plasma and serum OPN may be useful markers in the diagnosis of epithelial MPM in addition to traditional radiological exams. However, in our opinion plasma OPN is preferable to serum OPN because it is more stable and measurements of OPN in serum are less reliable.

In plain English

This Italian study measured the blood protein osteopontin in both plasma and serum. It asked whether osteopontin could help tell apart patients with epithelioid malignant pleural mesothelioma from people previously exposed to asbestos who did not have cancer. Plasma came from 94 healthy asbestos-exposed people, 113 people with benign respiratory disease and 32 consecutive mesothelioma patients treated in Pisa. Serum was tested in a subset. In handling tests, both plasma and serum levels fell with storage at minus 80 degrees C. Serum levels also changed with time at room temperature and dropped after one thawing. Average plasma and serum levels were significantly higher in mesothelioma patients than in either comparison group; no statistically significant difference was found between those two groups. At its best cutoff of 878.65 ng/mL, plasma osteopontin detected 68.8% of mesothelioma patients and correctly excluded 84.5% of the comparison subjects. For serum, the figures were 62.5% and 87.3%. In the non-cancer groups, levels showed no significant correlation with age, exposure duration or pack-years in current smokers. The authors concluded that plasma osteopontin is preferable to serum.

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: Diagnostic biomarker study comparing plasma and serum osteopontin (OPN), including laboratory tests of sample handling (preanalytic variables)
• Who was studied: 207 individuals with previous asbestos exposure (94 healthy controls and 113 patients with benign respiratory disease, BRD) and 32 consecutive patients with epithelioid malignant pleural mesothelioma (19 stage III, 13 stage II) treated at the University Hospital of Pisa, Italy. Serum OPN was measured in 80 healthy subjects, 92 BRD patients and 24 MPM patients. Handling tests used blood samples from 7 healthy controls.
• Exposure: Previous asbestos exposure, assessed by occupational questionnaire. Mean duration was 18.66 plus or minus 7.6 years, mostly in the chemistry, metal-mechanics and shipbuilding sectors. Fiber types were not reported.
• Main results:
  • Storage at -80°C for 1, 2 or 4 weeks significantly decreased both plasma and serum OPN levels.
  • Time at room temperature did not affect plasma OPN. Serum OPN differed significantly between 15 and 60 minutes at room temperature.
  • Serum OPN decreased significantly after the first thawing, while plasma OPN was stable up to the second thawing.
  • Mean plasma and serum OPN were significantly higher (p<0.0001) in epithelial MPM patients than in healthy subjects and BRD patients. Plasma means (ng/mL): MPM 1287.31 ± 1002.76 (n=32), healthy 549.36 ± 387.28 (n=94), BRD 512.08 ± 355.92 (n=113). Serum means: MPM 54.02 ± 77.26 (n=24), healthy 13.60 ± 22.25 (n=80), BRD 16.40 ± 26.07 (n=92).
  • No statistically significant difference was found between healthy subjects and BRD patients (plasma p=0.212, serum p=0.457).
  • For distinguishing MPM from controls, plasma OPN had an AUC of 0.780.
  • At the best plasma OPN cutoff of 878.65 ng/mL, sensitivity was 68.8% and specificity was 84.5%.
  • Serum OPN had an AUC of 0.725. At the best cutoff of 16.06 ng/mL, sensitivity was 62.5% and specificity was 87.3%.
  • Within the control group (healthy subjects and BRD patients), no significant correlation was found between plasma OPN and age, duration of asbestos exposure, or pack-years in current smokers. Serum OPN likewise showed no significant correlation with age, duration of asbestos exposure or pack-years.
  • In asbestos-exposed subjects, OPN levels showed no correlation with spirometry, DLCO, chest x-ray or CT results.
  • Among MPM patients, plasma OPN was 785.92±540.93 ng/mL at stage II and 1639.45±1108.69 ng/mL at stage III (p=0.019). Serum OPN was 16.53±16.56 ng/mL at stage II and 80.82±92.28 ng/mL at stage III (p=0.041).
  • Plasma and serum OPN measurements corresponded with each other (R2=0.28, p<0.0001).
• The authors' conclusion: The authors concluded that plasma OPN is preferable to serum OPN, although the two had similar sensitivity and specificity at their best cutoffs. They suggested that plasma OPN may have clinical and preventive use alongside radiology and possibly other biomarkers such as SMRP.

Topics

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

Medical terms in this study, explained in our Lexicon: Osteopontin, Pleural Mesothelioma, Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Asbestos Exposure, Confounding, Habit.

Related studies

• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• 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)
• Preliminary study of positron emission tomography/computed tomography and plasma osteopontin levels in patients with asbestos-related pleural disease — S. Kurata, M. Ishibashi, et al. (2010)
• Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers — M.K. Felten, K. Khatab, et al. (2014)
• 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)

Browse return to medical research.