Skip to main content
SpringerLink
Log in

Exploring Potential of RPPA Technique in Oral Cancer Biomarker Discovery Research

  • Chapter
  • First Online:
Molecular Diagnostics in Cancer Patients

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomark Prev. 2016;25:16–27. https://doi.org/10.1158/1055-9965.EPI-15-0578.

    Article  Google Scholar 

  2. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86. https://doi.org/10.1002/ijc.29210.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  4. Fukuda M, Kusama K, Sakashita H. Molecular insights into the proliferation and progression mechanisms of the oral cancer: strategies for the effective and personalized therapy. Jpn Dent Sci Rev. 2012;48:23–41. https://doi.org/10.1016/j.jdsr.2011.08.001.

    Article  Google Scholar 

  5. Mangalath U, Aslam S, Kooliyat AH, Khader A, Francis PG, Mikacha SK, et al. Recent trends in prevention of oral cancer. J Int Prev Commun Dent. 2014;4:S131–8. https://doi.org/10.4103/2231-0762.149018.

    Article  Google Scholar 

  6. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74. https://doi.org/10.1016/j.cell.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  7. Sethi S, Ali S, Philip PA, Sarkar FH. Clinical advances in molecular biomarkers for cancer diagnosis and therapy. Int J Mol Sci. 2013;14:14771–84. https://doi.org/10.3390/ijms140714771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5:463–6. https://doi.org/10.1097/COH.0b013e32833ed177.

    Article  PubMed  PubMed Central  Google Scholar 

  9. William B, Ronald BH. Characteristics of the ideal tumor marker in Hollandfrei cancer medicine. 6th ed. Hamilton: BC, Decker; 2003.

    Google Scholar 

  10. Carr KM, Rosenblatt K, Petricoin EF, Liotta LA. Genomic and proteomic approaches for studying human cancer: prospects for true patient-tailored therapy. Hum Genomics. 2004;1:134–40. https://doi.org/10.1186/1479-7364-1-2-134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Shruthi BS, Vinodhkumar P, Selvamani. Proteomics: a new perspective for cancer. Adv Biomed Res. 2016;5:67. https://doi.org/10.4103/2277-9175.180636.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gallagher RI, Espina V. Reverse phase protein arrays: mapping the path towards personalized medicine. Mol Diagn Ther. 2014;18:619–30. https://doi.org/10.1007/s40291-014-0122-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Maes E, Mertens I, Valkenborg D, Pauwels P, Rolfo C, Baggerman G. Proteomics in cancer research: are we ready for clinical practice? Crit Rev Oncol Hematol. 2015;96:437–48. https://doi.org/10.1016/j.critrevonc.2015.07.006.

    Article  PubMed  Google Scholar 

  14. Hudler P, Kocevar N, Komel R. Proteomic approaches in biomarker discovery: new perspectives in cancer diagnostics. Sci World J. 2014;2014:260348. https://doi.org/10.1155/2014/260348.

    Article  CAS  Google Scholar 

  15. Mordente A, Meucci E, Martorana GE, Silvestrini A. Cancer biomarkers discovery and validation: state of the art, problems and future perspectives. Adv Exp Med Biol. 2015;867:9–26. https://doi.org/10.1007/978-94-017-7215-0_2.

    Article  CAS  PubMed  Google Scholar 

  16. Parker CE, Borchers CH. Mass spectrometry based biomarker discovery, verification, and validation—quality assurance and control of protein biomarker assays. Mol Oncol. 2014;8:840–58. https://doi.org/10.1016/j.molonc.2014.03.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Masuda M, Yamada T. Signaling pathway profiling using reverse-phase protein array and its clinical applications. Expert Rev Proteomics. 2017;14:607–15. https://doi.org/10.1080/14789450.2017.1344101.

    Article  CAS  PubMed  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.

    Article  CAS  PubMed  Google Scholar 

  19. Mueller C, Liotta LA, Espina V. Reverse phase protein microarrays advance to use in clinical trials. Mol Oncol. 2010;4:461–81. https://doi.org/10.1016/j.molonc.2010.09.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Huang Y, Zhu H. Protein array-based approaches for biomarker discovery in cancer. Genomics Proteomics Bioinformatics. 2017;15:73–81. https://doi.org/10.1016/j.gpb.2017.03.001.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Tanase C, Albulescu R, Neagu M. Proteomic approaches for biomarker panels in cancer. J Immunoassay Immunochem. 2016;37:1–15. https://doi.org/10.1080/15321819.2015.1116009.

    Article  CAS  PubMed  Google Scholar 

  22. Wachter A, Bernhardt S, Beissbarth T, Korf U. Analysis of reverse phase protein array data: from experimental design towards targeted biomarker discovery. Microarrays. 2015;4:520–39. https://doi.org/10.3390/microarrays4040520.

    Article  CAS  PubMed  PubMed Central  Google 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen Y, Azman SN, Kerishnan JP, Zain RB, Chen YN, Wong Y-L, et al. Identification of host-immune response protein candidates in the sera of human oral squamous cell carcinoma patients. PLoS One. 2014;9:e109012. https://doi.org/10.1371/journal.pone.0109012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chen B, Liu Y, Shen Y, Xia Z, He G, Liang S. Protein microarrays in proteome-wide applications. J Proteomics Bioinform. 2014;S12:001. https://doi.org/10.4172/jpb.S12-001.

    Article  Google Scholar 

  26. Creighton CJ, Huang S. Reverse phase protein arrays in signaling pathways: a data integration perspective. Drug Des Devel Ther. 2015;9:3519–27. https://doi.org/10.2147/DDDT.S38375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ni YH, Ding L, Hu QG, Hua ZC. Potential biomarkers for oral squamous cell carcinoma: proteomics discovery and clinical validation. Proteomics Clin Appl. 2015;9:86–97. https://doi.org/10.1002/prca.201400091.

    Article  CAS  PubMed  Google Scholar 

  28. Sawant S, Vaidya M, Chaukar D, Alam H, Dmello C, Gangadaran P, et al. Clinical significance of aberrant vimentin expression in oral premalignant lesions and carcinomas. Oral Dis. 2014;20(5):453–65. https://doi.org/10.1111/odi.12151.

    Article  CAS  PubMed  Google Scholar 

  29. Kaur J, Jacobs R, Huang Y, Salvo N, Politis C. Salivary biomarkers for oral cancer and pre-cancer screening: a review. Clin Oral Investig. 2018;22:633–40. https://doi.org/10.1007/s00784-018-2337-x.

    Article  CAS  PubMed  Google 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.

    Article  CAS  PubMed  Google 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 

  32. Rivera C, Oliveira AK, Costa RAP, De Rossi T, Paes Leme AF. Prognostic biomarkers in oral squamous cell carcinoma: a systematic review. Oral Oncol. 2017;72:38–47.

    Article  CAS  PubMed  Google Scholar 

  33. Chai YD, Zhang L, Yang Y, Su T, Charugundla P, Ai J, et al. Discovery of potential serum protein biomarkers for lymph node metastasis in oral cancer. Head Neck. 2016;38:118–25. https://doi.org/10.1002/hed.23870.

    Article  PubMed  Google Scholar 

  34. Rai V, Mukherjee R, Ghosh AK, Routray A, Chakraborty C. “Omics” in oral cancer: new approaches for biomarker discovery. Arch Oral Biol. 2018;87:15–34. https://doi.org/10.1016/j.archoralbio.2017.12.003.

    Article  CAS  PubMed  Google Scholar 

  35. Arellano-Garcia ME, Li R, Liu X, Xie Y, Yan X, Loo JA, et al. Identification of tetranectin as a potential biomarker for metastatic oral cancer. Int J Mol Sci. 2010;11:3106–21. https://doi.org/10.3390/ijms11093106.

    Article  CAS  PubMed  PubMed Central  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.

  37. Wu CC, Chu HW, Hsu CW, Chang KP, Liu HP. Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma. Proteomics. 2015;15:3394–404. https://doi.org/10.1002/pmic.201500157.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. DBT-BioCARE Women Scientist, Institute of Life Sciences, Bhubaneswar, Odisha, India

    Neera Singh

  2. Department of Health Research, Government of India, ICMR Regional Medical Research Centre, Bhubaneswar, Odisha, India

    Sanghamitra Pati

Authors
  1. Neera Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sanghamitra Pati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sanghamitra Pati .

Editor information

Editors and Affiliations

  1. Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India

    Kamla Kant Shukla

  2. Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India

    Praveen Sharma

  3. Department of Surgical Oncology, All India Institute of Medical Sciences, Jodhpur, India

    Sanjeev Misra

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Singh, N., Pati, S. (2019). Exploring Potential of RPPA Technique in Oral Cancer Biomarker Discovery Research. In: Shukla, K., Sharma, P., Misra, S. (eds) Molecular Diagnostics in Cancer Patients. Springer, Singapore. https://doi.org/10.1007/978-981-13-5877-7_16

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-5877-7_16

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-5876-0

  • Online ISBN: 978-981-13-5877-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation