Four-protein signature accurately predicts lymph node metastasis and survival in oral squamous cell carcinoma

Zanaruddin, S.N.S. and Saleh, A. and Yang, Y.H. and Hamid, S. and Mustafa, W.M.W. and Bariah, A. and Zain, R.B. and Lau, S.H. and Cheong, S.C. (2013) Four-protein signature accurately predicts lymph node metastasis and survival in oral squamous cell carcinoma. Human Pathology, 44 (3). pp. 417-426. ISSN 0046-8177, DOI


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The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (NO) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (BER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5 and a sensitivity of 70, with a prognostic accuracy of 83.4 for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P = .036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC. (C) 2013 Elsevier Inc. All rights reserved.

Item Type: Article
Additional Information: ISI Document Delivery No.: 092MI Times Cited: 0 Cited Reference Count: 34 Zanaruddin, Sharifah Nurain Syed Saleh, Amyza Yang, Yi-Hsin Hamid, Sharifah Mustafa, Wan Mahadzir Wan Bariah, A. A. N. Khairul Zain, Rosnah Binti Lau, Shin Hin Cheong, Sok Ching Ministry of Science, Technology and Innovation, Putrajaya, Malaysia 06-00-00-000; University of Malaya, Kuala Lumpur, Malaysia J-00000-73561; Cancer Research Initiatives Foundation This study was funded by the Ministry of Science, Technology and Innovation, Putrajaya, Malaysia (grant no. 06-00-00-000), High Impact Research (HIR) grant from University of Malaya, Kuala Lumpur, Malaysia (J-00000-73561), and other sponsors of the Cancer Research Initiatives Foundation. W b saunders co-elsevier inc Philadelphia
Uncontrolled Keywords: Lymph node metastasis Oral squamous cell carcinoma Biomarkers Prognostic signature Survival tissue microarrays expression profile gene-expression neck head overexpression cancer cavity involvement ultrasound
Subjects: R Medicine > RK Dentistry
Divisions: Faculty of Dentistry > Dept of Oral Pathology & Oral Medicine & Periodontology
Depositing User: Mr Ahmad Azwan Azman
Date Deposited: 11 Jul 2013 04:32
Last Modified: 29 Oct 2014 00:45

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