Exploring Potential of RPPA Technique in Oral Cancer Biomarker Discovery Research
Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related mortality worldwide. India has one of the highest incidence rates of oral cancer due to extremely popular use of different forms of smokeless tobacco like areca-nut and betel-leaf chewing habits. Delayed detection is one of the major contributing factors for higher morbidity rate among oral cancer patients. Despite new innovations in surgery, radiation, and chemotherapy, the prognosis for OSCC patients remains poor, with the lowest 5-year survival rate (40–50%). Presently, there are no effective molecular markers available for earlier screening of oral cancer. The gold standard for diagnosis of OSCC is the conventional oral examination followed by histopathological analysis of biopsy from the suspicious lesions. Detection of cancerous lesions by invasive method like biopsy is often associated with patient discomfort and reluctance for further follow-ups. Therefore, it is critical to develop non-invasive diagnostic methods for earlier screening of oral cancers for improved survival rate. In complex disorders like cancer, genetic alterations do not always correlate with the disease causes. Changes in protein structure and expression levels play an important role in tumor development and progression. Thus, undoubtedly proteins are attractive molecular targets as potential biomarkers due to the fact that they participate more actively in cellular activities than DNA and RNA. Proteomics holds a great promise for the discovery of proteins that may be used as biomarkers for the early detection of various cancers. Salivary diagnostics is a rapidly advancing field that offers clinicians and patients the potential of rapid, noninvasive diagnostics with excellent accuracy. The chapter describes various proteomics approaches utilized for the biomarker discovery of oral cancer in both tissues and saliva with a special focus on application of Reverse Phase protein array (RPPA) in oral cancer. RPPA is a novel, high throughput technique that can perform robust quantification using nanolitres of protein lysates. RPPA being a highly sensitive and specific technique has been successfully used in biomarker discovery, personalized therapy and to study differential protein expression pattern and post-translational modifications in various cancers.
KeywordsOral cancer RPPA Protein Biomarker Diagnosis
- 3.Petersen PE. Oral cancer prevention and control—the approach of the World Health Organization. Oral Oncol. 2009;45:454–60. https://doi.org/10.1016/j.oraloncology.2008.05.023.CrossRefPubMedGoogle Scholar
- 9.William B, Ronald BH. Characteristics of the ideal tumor marker in Hollandfrei cancer medicine. 6th ed. Hamilton: BC, Decker; 2003.Google Scholar
- 18.Paweletz CP, Charboneau L, Bichsel VE, Simone NL, Chen T, Gillespie JW, et al. Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front. Oncogene. 2001;20:1981–9. https://doi.org/10.1038/sj.onc.1204265.CrossRefPubMedGoogle Scholar
- 23.Akbani R, Becker KF, Carragher N, Goldstein T, de Koning L, Korf U, et al. Realizing the promise of reverse phase protein arrays for clinical, translational, and basic research: a workshop report: the RPPA (Reverse Phase Protein Array) Society. Mol Cell Proteomics. 2014;13:1625–43. https://doi.org/10.1074/mcp.O113.034918.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Dey KK, Pal I, Bharti R, Dey G, Kumar BN, Rajput S, et al. Identification of RAB2A and PRDX1 as the potential biomarkers for oral squamous cell carcinoma using mass spectrometry-based comparative proteomic approach. Tumour Biol. 2015;36:9829–37. https://doi.org/10.1007/s13277-015-3758-7.CrossRefPubMedGoogle Scholar
- 31.Huang TT, Chen JY, Tseng CE, Su YC, Ho HC, Lee MS, et al. Decreased GRP78 protein expression is a potential prognostic marker of oral squamous cell carcinoma in Taiwan. J Formos Med Assoc. 2010;109: 326–37. doi: 10.1016/S0929-6646(10)60060-5.Google Scholar
- 36.Bhattarai BP, Klongnoi B, Khovidhunkit SP, Wongsirichat, Natthamet. Protein biomarker in saliva in oral squamous cell carcinoma. SWU Dent J. 2017;10:13. https://www.researchgate.net/publication/322832732_protein_biomarker_in_saliva_in_oral_squamous_cell_carcinoma. Accessed 20 Mar 2018.