Cancer survival and prognosis are dependent upon how early the cancer is discovered and the ability to fine-tune treatments to that particular cancer. A cancer biomarker for a specific tumor type can provide vital information needed to successfully treat cancer. The ultimate goal in the discovery of biomarkers is to enhance the survivability of cancer through improved diagnostics and treatments.
Those diagnosed with one type of cancer, oral squamous cell carcinoma (OSCC), can greatly benefit from the discovery of a new cancer biomarkers. This type of cancer is often undiagnosed until the later stages. The 5-year survival rate for this cancer remains low, and it also has a high rate of reoccurrence, especially in cases where it has metastasized to other areas of the neck.1,2
OSCC is typically discovered by dentists and requires an invasive biopsy to confirm suspected legions. Hu et al. were able to validate five promising biomarkers, including including Mac-2 binding protein (M2BP), myeloid related protein 14 (MRP14), CD59, profilin 1, and catalase, which were present in human saliva.3
The Hu group investigated 64 OSCC patients matched with 64 healthy controls. One group of participants (n = 16) was profiled using shotgun proteomics based on C4 reversed-phase liquid chromatography for prefractionation. They also employed capillary reversed-phase liquid chromatography with quadruple time-of-flight mass spectrometry and Mascot sequence database searching.
Immunoassays further validated the candidate biomarkers using the remaining 48 patients and controls. The combination of these candidate biomarkers yielded a receiver operating characteristic value of 93%, sensitivity of 90%, and specificity of 83% in detecting OSCC.
Other groups studying oral cancers have identified myosin and actin as biomarkers in distinguishing between malignant and premalignant lesions.4 Salivary transferrin has also shown to be a biomarker for the early detection of oral cancers.5
In a review publication,6 Shah et al. have reported on many examples of biomarkers found for oral cancers. This publication also included biomarker findings from their own lab. The Shah lab also reported on the results on a project in collaboration with the University of California at Los Angeles (UCLA) to develop an electrochemical (EC) sensor, which simultaneously detects multiple salivary biomarkers for oral cancer.7
A multiplex assay of IL-8 mRNA and IL-8 protein levels measured by the EC sensor showed significant differences between oral cancer patients and healthy controls, with as high as a 90% sensitivity and specificity for both IL-8 mRNA and IL-8. The results were further validated using traditional experiments using the same saliva samples, which included enzyme-linked immunosorbent assay, ELISA and polymerase chain reaction.
The EC sensor could lead to the development of a point-of-care tool for diagnosing oral cancer. The use of proteomics techniques in the discovery of biomarkers for oral cancer looks very promising and will likely lead to future advances and discoveries, thereby enhancing the survivability and quality of life for patients diagnosed with oral cancer.
1. Lippman, S.M. (2001) ‘Molecular markers of the risk of oral cancer‘, New England Journal of Medicine, 2001 (344), (pp. 1323-1326)
2. Vokes, E. (1993) ‘Head and neck cancer‘, New England Journal of Medicine, 328 (3), (pp. 184-194)
3. Hu, S., et al. (2008) ‘Salivary proteomics for oral cancer biomarker discovery‘, Clinical Cancer Research, 14 (19), (pp. 6246-6252)
4. de Jong, E.P., et al, (2010) ‘Quantitative proteomics reveals myosin and actin as promising saliva biomarkers for distinguishing pre-malignant and malignant oral lesions‘, PLoS One, 5 (6), (p. e11148)
5. Jou, Y.J., et al. (2010) ‘Proteomic identification of salivary transferrin as a biomarker for early detection of oral cancer‘, Analytica Chimica Acta, 681 (1-2), (pp. 41-48)
6. Shah, F.D., et al. (2011) ‘A review on salivary genomics and proteomics biomarkers in oral cancer‘, Indian Journal of Clinical Biochemistry, 26 (4), (pp. 326-334)
7. Wei, F., et al. (2009) ‘Electrochemical sensor for multiplex biomarkers detection‘, Clinical Cancer Reserch 15 (13), (4446-4452)