Abstract 5161: Discovery of a matrix metalloproteinase MMP10 as a clinically relevant biomarker to predict lymph node metastasis in tongue squamous cell carcinoma

Abstract

Abstract Background: Oral cancer is the leading malignancy in Indian men. About 70% of patients present in clinical T1 and 30% in T4 stage that have clinically lymph node negative (N0) neck examination at the time of presentation. However, the current standard of care is to perform potentially mutilating and morbid neck dissection in all patients irrespective of their nodal status, because of a 27% chance of having pathologically involved lymph nodes. Therefore, its an imperative to find accurate predictors of pathological lymph node status, whereby a considerable fraction can be spared unnecessary surgery. Material and Methods: We report an integrated analysis of whole transcriptome and miRNA expression profiling of primary tongue squamous cell carcinomas (TSCC) to identify clinically relevant molecular biomarkers to predict lymph node metastases. Differential expression of transcriptome was performed using tophat-cufflinks-cummeRbund pipeline and miRNA using standard array data analysis pipeline. Alterations identified were validated using orthologous technologies in an extended cohort of tongue squamous cell carcinoma patients. Finally, we present functional validation of the candidate genes using biochemical analysis and cell-based assay. Results: We investigated simultaneously the transcriptional changes of miRNA and mRNA expression levels of eleven N0 and N+ TSCC, and six paired control samples. To examine global miRNA and mRNA expression patterns, we perfomed an integrative analysis of whole transcriptome sequencing and miRNA expression profile of primary tumors. Linking expression profiles of whole transcriptome and miRNAs with their annotated functions, we find a negatively correlated network of 30 miRNA and 60 mRNA. We present here robust molecular validation of a novel and dynamic interplay of two miRNAs mir-944, mir-183-5p and a matrix metalloproteinase MMP10 expression, along with clinical correlation in an independent set of 40 primary N0 and N+ TSCC tumors to collectively predict nodal metastases in TSCC. Immunohistochemical validation of the candidate biomarker MPP10 among primary TSCC tumors to establish its utility in clinical settings will be discussed. Conclusion: Knowledge from integrated expression analysis along with functional validation identify a novel matrix metalloproteinase as a clinically relevant biomarker to prognosticate metastases in patients with early stage oral tongue cancers. Citation Format: Pawan Upadhyay, Nilesh Laxman Gardi, Hemant Ramesh Dhamne, Kavitha Sonawane, Anil D'Cruz, Sudhir Nair, Amit Dutt. Discovery of a matrix metalloproteinase MMP10 as a clinically relevant biomarker to predict lymph node metastasis in tongue squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5161. doi:10.1158/1538-7445.AM2015-5161