Written by Joyce Smith, BS. Research demonstrates that a combination of 3 biomarkers when used for cancer detection helps minimize false positives and negatives.

Malignant melanoma (MM) is a highly aggressive cancer that is increasing in numbers and offers a poor prognosis. [1, 2] There are no reliable diagnostic markers for early detection of this disease. The serum biomarker “soluble mesothelin-related proteins’ (SMRPs), is used most frequently [3, 4] but it has limited value for the early detection of MM because of its low sensitivity [5]. In this study, researchers combine two epigenetically regulated markers in MM, (miR126) and methylated thrombomodulin promoter (Met-TM), with SMRPs and evaluate their potential to detect early stage MM.

A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled. Serum samples were collected, and serum levels of the three biomarkers SMRPs, miR-126 and Met-TM were evaluated to establish a biomarker prediction model. The authors’ objective was to show that the biomarker SMRPs could be used as a sensitive and specific screening test for MM.

To validate the accuracy of this 3-biomarker prediction model, researchers investigated the diagnostic significance of changes in serum levels of miR126 and Met-TM in association with serum levels of SMRPs from 18 MM patients, 50 asbestos-exposed healthy individuals, 20 healthy controls and 42 lung cancer patients. The accuracy of these biomarkers and their cancer specificity was confirmed in a second validation cohort and lung cancer population.

Results:

The 3 biomarker model significantly differentiated MM patients from high-risk asbestos exposed individuals and healthy controls (P=0.047).

Conclusion:

The data from this study does not prove that the 3-biomarker combination can detect early MM; however, this combination of biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. It demonstrated that combining the biomarkers miR126 and Met-TM with SMRPs as a diagnosis for early MM, helped overcome the limitations of using SMRPs alone by minimized the false-negatives and false-positives.

Source: Santarelli, Lory, et al. “Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma.” Lung Cancer 90.3 (2015): 457-464.

© 2015 Elsevier Ireland Ltd. All rights reserved.

Posted November 3, 2015.

References:

  1. LaDou, J., et al., The case for a global ban on asbestos. Environmental health perspectives, 2010: p. 897-901.
  2. Vogelzang, N.J., et al., Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. Journal of Clinical Oncology, 2003. 21(14): p. 2636-2644.
  3. Robinson, B.W., et al., Mesothelin-family proteins and diagnosis of mesothelioma. The Lancet, 2003. 362(9396): p. 1612-1616.
  4. Scherpereel, A., et al., Soluble mesothelin–related peptides in the diagnosis of malignant pleural mesothelioma. American journal of respiratory and critical care medicine, 2006. 173(10): p. 1155-1160.
  5. Santarelli, L., et al., Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma. PloS one, 2011. 6(4): p. e18232.