Quantification of IRS-1 and akt levels in saliva of patient with OSCC
Abstract
Background: Oral squamous cell carcinoma (OSCC) remains a significant global health burden, often diagnosed at advanced stages. The Insulin receptor substrate-1 (IRS-1) and Akt signaling axis is a critical driver of cellular proliferation and survival in many malignancies. This study aimed to quantify the levels of IRS-1 and Akt in the saliva of OSCC patients and evaluate their potential as non-invasive diagnostic biomarkers.
Materials and Methods: In this case-control study, unstimulated whole saliva was collected from 30 histopathologically confirmed OSCC patients and 30 age- and sex-matched healthy controls. IRS-1 and Akt concentrations were quantified using high-sensitivity ELISA and normalized to total salivary protein content. Data were analyzed using independent samples t-tests, with significance set at p < 0.05.
Results: Salivary IRS-1 levels were significantly higher in OSCC patients (482.14 ± 84.56 pg/mg protein) compared to healthy controls (194.32 ± 42.18 pg/mg protein, p < 0.001). Similarly, salivary Akt levels were markedly elevated in the OSCC group (312.85 ± 62.34 pg/mg protein) compared to the control group (126.47 ± 28.92 pg/mg protein, p < 0.001). Furthermore, levels of both biomarkers were significantly higher in patients with advanced clinical stages (III/IV) compared to early-stage (I/II) disease (p < 0.01).
Conclusion: Salivary IRS-1 and Akt are significantly upregulated in OSCC and correlate with clinical disease progression. These findings suggest that the IRS-1/Akt signaling axis in saliva holds promise as a non-invasive diagnostic tool for the early detection and risk stratification of oral malignancy.
References
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34.
3. Farah CS. Molecular oncology of oral squamous cell carcinoma. Oral Oncol. 2018;86:141-57.
4. Altomare DA, Testa JR. Perturbations of the AKT signaling pathway in human cancer. Oncogene. 2005;24(50):7455-64.
5. Mardilovich K, Pankratz SL, Shaw LM. Expression and function of the insulin receptor substrate proteins in cancer. Cell Commun Signal. 2009;7:14.
6. Manning BD, Toker A. AKT/PKB Signaling: Navigating the Network. Cell. 2017;169(3):381-405.
7. Gibson SL, Ma Z, Shaw LM. The insulin receptor substrate-1 (IRS-1) adapter protein is required for Rho-dependent and -independent mesenchymal-like chemotaxis. Mol Cell Biol. 2007;27(1):350-65.
8. Pfaffe T, Cooper-White J, Beyerlein P, Kostner K, Punyadeera C. Diagnostic potential of saliva: current state and future applications. Clin Chem. 2011;57(5):675-87.
9. Yoshizawa JM, Schafer CA, Schafer JJ, Farrell JJ, Paster BJ, Wong DT. Salivary biomarkers: toward future clinical and diagnostic utilities. Clin Microbiol Rev. 2013;26(4):781-91.
10. Saheb Jamee M, Booorboor Shirkhani M, Modarressi MH. Salivary biomarkers in oral squamous cell carcinoma: a review of the literature. J Oral Pathol Med. 2015;44(8):561-72.
11. Arellano-Garcia ME, Li R, Liu X, Liao W, Zhou X, Wong DT. A database of salivary biomarkers for oral squamous cell carcinoma. Oral Oncol. 2010;46(2):102-7.
12. Roi A, Rusu LC, Roi CI, Luca RE, Boia S, Munteanu RI. A New Approach for the Diagnosis of Systemic and Oral Diseases based on Salivary Biomarkers. Dis Markers. 2019;2019:8761860.
13. Cheng YS, Rees T, Jordan L. Salivary biomarkers for squamous cell carcinoma of the oral cavity. Curr Opin Otolaryngol Head Neck Surg. 2014;22(2):117-26.
14. Yakob M, Fuentes L, Wang MB, Abemayor E, Wong DT. Salivary biomarkers for detection of oral squamous cell carcinoma - current state and recent advances. Oral Oncol. 2014;50(11):1037-42.
15. Dearth RK, Cui X, Kim HJ, Hadsell DL, Lee AV. Mammary development and tumorigenesis in mice overexpressing insulin receptor substrate 1 (IRS-1). Transgenic Res. 2006;15(2):125-33.
16. Clark AS, West K, Streicher S, Dennis PA. Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther. 2002;1(9):707-17.
17. Reuveni H, Flashner-Abramson E, Steiner L, et al. Therapeutic destruction of insulin receptor substrates for cancer treatment. Cancer Res. 2013;73(14):4383-94.
18. Gallo A, Tandon M, Alevizos I, Illei GG. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One. 2012;7(3):e30679.
19. Karar J, Maity A. PI3K/AKT/mTOR Pathway in Angiogenesis. Front Mol Neurosci. 2011;4:51.
20. Shpitzer T, Bahar G, Feinmesser R, Nagler RM. A comprehensive salivary analysis for oral cancer diagnosis. J Cancer Res Clin Oncol. 2007;133(9):613-7.
21. Hu S, Loo JA, Wong DT. Human body fluid proteome analysis. Proteomics. 2006;6(23):6326-53.
22. Massion PP, Taflan PM, Shyr Y, et al. Early involvement of the phosphatidylinositol 3-kinase/Akt pathway in lung cancer progression. Am J Respir Crit Care Med. 2004;170(10):1088-94.
23. Gual P, Le Marchand-Brustel Y, Tanti JP. Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochimie. 2005;87(1):99-109.
24. Castaneda FE, Walia B, Vijay-Kumar M, et al. Targeted deletion of metalloproteinase 9 sets the stage for potently exacerbating colitis in mice by molecular mechanisms that involve the Insulin-like growth factor I receptor. J Biol Chem. 2005;280(46):38539-49.
25. Kujan O, Shearston K, Farah CS. The role of salivary biomarkers in oral cancer detection and monitoring: an update. Dent J (Basel). 2016;4(2):15.

