Identification of RAB2A and PRDX1 as the potential biomarkers for oral squamous cell carcinoma using mass spectrometry-based comparative proteomic approach
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Despite the recent advances in diagnostic and therapeutic strategies, oral squamous cell carcinoma (OSCC) remains a major health burden. Protein biomarker discovery for early detection will help to improve patient survival rate in OSCC. Mass spectrometry-based proteomics has emerged as an excellent approach for detection of protein biomarkers in various types of cancers. In the current study, we have used 4-Plex isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun quantitative proteomic approach to identify proteins that are differentially expressed in cancerous tissues compared to normal tissues. The high-resolution mass spectrometric analysis resulted in identifying 2,074 proteins, among which 288 proteins were differentially expressed. Further, it was noticed that 162 proteins were upregulated, while 125 proteins were downregulated in OSCC-derived cancer tissue samples as compared to the adjacent normal tissues. We identified some of the known molecules which were reported earlier in OSCC such as MMP-9 (8.4-fold), ZNF142 (5.6-fold), and S100A7 (3.5-fold). Apart from this, we have also identified some novel signature proteins which have not been reported earlier in OSCC including ras-related protein Rab-2A isoform, RAB2A (4.6-fold), and peroxiredoxin-1, PRDX1 (2.2-fold). The immunohistochemistry-based validation using tissue microarray slides in OSCC revealed overexpression of the RAB2A and PRDX1 gene in 80 and 68 % of the tested clinical cases, respectively. This study will not only serve as a resource of candidate biomarkers but will contribute towards the existing knowledge on the role of the candidate molecules towards disease progression and therapeutic potential.
KeywordsiTRAQ Oral squamous cell carcinoma OSCC RAB2A PRDX1
We thank the Indian Council of Medical Research (3/2/2/207/2013/NCD-III) and the Department of Science and Technology (SR/SO/BB-58/2008) Government of India for financial support.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Conflicts of interest
- 8.Marimuthu A, Chavan S, Sathe G, Sahasrabuddhe NA, Srikanth SM, Renuse S, et al. Identification of head and neck squamous cell carcinoma biomarker candidates through proteomic analysis of cancer cell secretome. Biochim Biophys Acta. 2013;1834(11):2308–16. doi: 10.1016/j.bbapap.2013.04.029.CrossRefPubMedGoogle Scholar
- 10.Syed N, Chavan S, Sahasrabuddhe NA, Renuse S, Sathe G, Nanjappa V, et al. Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma. Proteomics. 2015;15(2-3):383–93. doi: 10.1002/pmic.201400338.CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Chiang WF, Hwang TZ, Hour TC, Wang LH, Chiu CC, Chen HR, et al. Calreticulin, an endoplasmic reticulum-resident protein, is highly expressed and essential for cell proliferation and migration in oral squamous cell carcinoma. Oral Oncol. 2013;49(6):534-–41. doi: 10.1016/j.oraloncology.2013.01.003.CrossRefPubMedGoogle Scholar
- 36.Kim JH, Bogner PN, Ramnath N, Park Y, Yu J, Park YM. Elevated peroxiredoxin 1, but not NF-E2-related factor 2, is an independent prognostic factor for disease recurrence and reduced survival in stage I non-small cell lung cancer. Clin Cancer Res. 2007;13(13):3875–82. doi: 10.1158/1078-0432.CCR-06-2893.CrossRefPubMedGoogle Scholar
- 38.Kim YJ, Lee WS, Ip C, Chae HZ, Park EM, Park YM. Prx1 suppresses radiation-induced c-Jun NH2-terminal kinase signaling in lung cancer cells through interaction with the glutathione S-transferase Pi/c-Jun NH2-terminal kinase complex. Cancer Res. 2006;66(14):7136–42. doi: 10.1158/0008-5472.CAN-05-4446.CrossRefPubMedGoogle Scholar