Resistance/response molecular signature for oral tongue squamous cell carcinoma

Article type: Research Article

Authors: Suresh, Amritha | Vannan, Muhil | Kumaran, Dhanya | Gümüs, Zeynep H. | Sivadas, Priya | Murugaian, Elango Erode | Kekatpure, Vikram | Iyer, Subramanian | Thangaraj, Kumarasamy | Kuriakose, Moni Abraham

Affiliations: Head and Neck Oncology Services, Mazumdar Shaw Cancer Centre, Narayana Hrudayalaya Foundations, Bangalore, India | Head and Neck Surgery, Amrita Institute of Medical Sciences and Research Centre, Kochi, India | Department of Physiology and Biophysics and HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY, USA | Department of Molecular Diagnostics, Mazumdar Shaw Cancer Centre, Narayana Hrudayalaya Foundations, Bangalore, India | Centre for Cellular and Molecular Biology, Hyderabad, India

Note: [] Corresponding author: Dr. Moni A Kuriakose MD FRCS, Professor and Director, Surgical Oncology, Chief, Head and Neck Oncology, Mazumdar Shaw Cancer Centre, Narayana Hrudayalaya, Bommasandra Indl Area, Anekal Taluk, Bangalore, 560099 India. Tel.: +91 080 22142229; Fax: +91 080 22142228; E-mail: mak12@nyu.edu

Abstract: Worldwide, the incidence of oral tongue cancer is on the rise, adding to the existing burden due to prevailing low survival and high recurrence rates. This study uses high-throughput expression profiling to identify candidate markers of resistance/response in patients with oral tongue cancer. Analysis of primary and post-treatment samples (12 tumor and 8 normal) by the Affymetrix platform (HG U133 plus 2) identified 119 genes as differentially regulated in recurrent tumors. The study groups had distinct profiles, with induction of immune response and apoptotic pathways in the non-recurrent and metastatic/invasiveness pathways in the recurrent group. Validation was carried out in tissues by Quantitative Real-Time PCR (QPCR) (n=30) and immunohistochemistry (IHC) (n=35) and in saliva by QPCR (n=37). The markers, COL5A1, HBB, IGLA and TSC individually and COL5A1 and HBB in combination had the best predictive power for treatment response in the patients. A subset of markers identified (COL5A1, ABCG1, MMP1, IL8, FN1) could be detected in the saliva of patients with oral cancers with their combined sensitivity and specificity being 0.65 and 0.87 respectively. The study thus emphasizes the extreme prognostic value of exploring markers of treatment resistance that are expressed in both tissue and saliva.

Keywords: Tongue cancer, resistance, response, micro array, gene expression, saliva, biomarkers

DOI: 10.3233/DMA-2012-0860

Journal: Disease Markers, vol. 32, no. 1, pp. 51-64, 2012