Profiling tumor-associated markers for early detection of malignant mesothelioma: an epidemiologic study

Our plain-English summary of Profiling tumor-associated markers for early detection of malignant mesothelioma: an epidemiologic study, by M. Amati, M. Tomasetti, M. Scartozzi, et al (Cancer Epidemiology, Biomarkers & Prevention, 2008).

The study

• Authors: M. Amati, M. Tomasetti, M. Scartozzi, L. Mariotti, R. Alleva, E. Pignotti, B. Borghi, M. Valentino, M. Governa, J. Neuzil, L. Santarelli
• Journal: Cancer Epidemiology, Biomarkers & Prevention
• Published: 2008;17(1):163-70
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Improved detection methods for diagnosis of asymptomatic malignant mesothelioma (MM) are essential for an early and reliable detection and treatment of this type of neoplastic disease. Thus, focus has been on finding tumor markers in the blood that can be used for noninvasive detection of MM. Ninety-four asbestos-exposed subjects defined at high risk, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the clinical significance of 8-hydroxy-2'-deoxyguanosine (8OHdG) in WBCs and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors [platelet-derived growth factor beta, hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor beta (VEGFbeta)], and matrix proteases [matrix metalloproteinase (MMP) 2, MMP9, tissue inhibitor of metalloproteinase (TIMP) 1, and TIMP2] for potential early detection of MM. The area under receiver operating characteristic (ROC) curves indicate that 8OHdG levels can discriminate asbestos-exposed subjects from healthy controls but not from MM patients. Significant area under ROC curve values were found for SMRPs, discriminating asbestos-exposed subjects from MM patients but not from healthy controls. Except for platelet-derived growth factor beta, the hepatocyte growth factor, basic fibroblast growth factor, and VEGFbeta can significantly differentiate high-risk individuals from healthy control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, and TIMP2. In addition to the diagnostic performance defined by the ROC analysis, the sensitivity and specificity results of markers with clinical significance were calculated at defined cutoffs. The combination of 8OHdG, VEGFbeta, and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.

In plain English

This Italian study compared blood markers in three groups: 94 men with a history of asbestos exposure who had worked in shipbuilding, 54 age-matched people never exposed to asbestos, and 22 patients with malignant mesothelioma (MM) diagnosed on pleural biopsies. Patients with MM had higher plasma levels of soluble mesothelin-related peptides (SMRPs) than both other groups. SMRP levels in the exposed workers did not differ significantly from those in controls. 8OHdG, a marker of oxidative DNA damage measured in white blood cells, was higher in both the exposed workers and the MM patients than in controls. It did not significantly separate exposed workers from MM patients. The growth factors HGF, bFGF and VEGF-beta separated exposed workers from both controls and MM patients. MMP2, MMP9, TIMP1 and TIMP2 showed no diagnostic value. Combining 8OHdG with VEGF-beta raised the area under the curve for telling exposed workers from controls to 0.925 (plus or minus 0.035). The authors concluded that blood markers plus radiographic findings could be used to stratify mesothelioma risk in exposed populations, and that larger prospective studies are needed.

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: Cross-sectional comparison of blood biomarker levels among three groups (asbestos-exposed subjects, unexposed controls, mesothelioma patients), with ROC (diagnostic accuracy) analysis
• Who was studied: 94 male subjects with a history of asbestos exposure, all past or present shipbuilding workers, enrolled November 2004 to September 2005 in Ancona, Italy (response rate 19%; 500 letters sent). 54 age-matched controls never exposed to asbestos (33 men, 21 women), recruited November 2004 to January 2007. 22 MM patients (18 men, 4 women), diagnosed on pleural biopsies at the Oncology Clinic of the University Hospital of Ancona, recruited November 2004 to January 2007.
• Exposure: Occupational asbestos dust exposure in the shipbuilding industry, on average for more than 20 years. Fiber types are not stated.
• Main results:
  • MM patients had higher plasma SMRP levels than both the asbestos-exposed group and the control group. Mean levels were 10.9 plus or minus 16.2 nmol/L in MM patients, 1.7 plus or minus 6.0 in exposed subjects, and 1.1 plus or minus 1.5 in controls.
  • SMRP levels in asbestos-exposed subjects were not significantly different from those in age-matched controls (AUC 0.459, P = 0.502). SMRPs separated MM patients from controls (AUC 0.920) and from exposed subjects (AUC 0.927). The authors stated SMRPs can be proposed for diagnosis of existing MM but not to predict the disease.
  • White blood cell 8OHdG levels were higher in the asbestos-exposed group (mean 8.4 arbitrary units) and the MM group (9.2) than in controls (5.1). 8OHdG distinguished exposed subjects from controls with an AUC of 0.775 (P = 0.001).
  • 8OHdG did not significantly distinguish asbestos-exposed subjects from MM patients (AUC 0.556, P = 0.536).
  • HGF, bFGF and VEGF-beta significantly distinguished the asbestos-exposed (high-risk) subjects from both healthy controls and MM patients.
  • PDGF-beta distinguished MM patients from controls and from exposed subjects, but not exposed subjects from controls (AUC 0.534, P = 0.632).
  • MMP2, MMP9, TIMP1 and TIMP2 showed no diagnostic value.
  • For distinguishing asbestos-exposed subjects from controls (not for predicting who develops MM), combining 8OHdG with VEGF-beta gave an AUC of 0.925 plus or minus 0.035. The AUC was 0.775 plus or minus 0.037 for 8OHdG alone and 0.714 plus or minus 0.062 for VEGF-beta alone.
• The authors' conclusion: The authors concluded that combining blood biomarkers with radiographic findings could be used to stratify the risk of MM in asbestos-exposed populations.
• Limitations the authors state:
  • The authors stated that the biomarkers' value for predicting MM and for its clinical presentation needs validation in larger prospective studies.
  • 8OHdG was measured in white blood cells, which stand in for the target cells, rather than in mesothelial cells.
  • The authors stated that the value of 8OHdG levels for predicting cancer in an individual person is questionable.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Tumor Marker, Soluble Mesothelin-Related Peptides (SMRP), Platelet-Derived Growth Factor (PDGF), Fibroblast, Biomarker, Mesothelioma.

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