Abstract 3875: Proteome-wide approach to identify novel biomarkers in oral tumorigenesis

Abstract

Abstract Oral cancer is the most common type of intraoral head and neck cancer in humans, with a worldwide prevalence of more than 400,000 cases. In India, oral cancer ranks in top three in comparison with other cancer types. The majority of oral cancer patients are diagnosed at an advanced disease stage. Although, there have been many advances in oral cancer treatment, the overall survival rate of oral cancer patients only improved marginally over the past 30 years. The treatment regimen of oral cancer is mainly based on the tumor, node and metastasis (TNM) classification and histopathological diagnosis. These methods are subjective and often have low sensitivity to detect the disease in early stages. Hence, there is an urgent need for early diagnosis to develop biomarkers; to identify high risk individuals, to improve cancer detection at early stages, to predict disease outcome and response to therapy. Proteomics have been successfully employed in studies of lung, breast, prostate, gastrointestinal cancer, and head and neck squamous cell carcinoma. Reports are not much available to describe well characterized biomarkers which will aid for early detection of oral cancer. Racial differences were reported in many cancers including its morbidity, mortality, treatment response and survival rates. In Indian patient population, there is a significant knowledge gap exists in utilizing proteomics for biomarker discovery. The aim of this study is to identify novel candidate genes which may be used as prognostic or diagnostic biomarkers for Indian oral squamous cell carcinoma. The tongue tumor and adjacent normal samples were subjected to 2D - Differential in Gel Electrophoresis (2D-DIGE). Differentially expressed proteins in tumor samples were identified using nano-LC-MS/MS and validated by quantitative real time PCR. We found 800 protein spots were differentially expressed and seventy proteins were identified by mass spectrometry. Among them twelve proteins including Myosin isoforms, hemoglobin beta, Annexin A1, Creatinine kinase, Carbonic anhydrase, HSPA8 showed decreased expression while eighteen proteins including Apolipoprotein A1, HSPA5, Alpha 1 antitrypsin, Annexin isoforms, Peptidyl prolyl cis trans isomerase, Serpin isoforms, Tropomyosin, Thioredoxin, Alpha enolase, Calpain, Glutathione S Transferase, Heat shock protein beta 1, S100 isoforms showed increased expression in tongue tumor tissues. Most of the differentially regulated proteins were known to be involved in calcium homeostasis, cell cycle, cell growth and migration. The major outcome of this study was the identification of novel protein molecules which might be used as predictive, prognostic and diagnostic biomarkers for oral cancer. These proteins can also serve as a therapeutic intervention targets for oral cancer progression. This study would be the first study to map the whole proteome profile of the cancerous as well as normal tongue cheek tissue in Indian scenario. Citation Format: Sivagnanam Ananthi, Naga Padma Lakshmi CH, Anbarasu K, Mahalingam Sundarasamy. Proteome-wide approach to identify novel biomarkers in oral tumorigenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3875.