Meta-analysis of microRNAs expression in head and neck cancer: uncovering association with outcome and mechanisms

Joshua Lubov, Mariana Maschietto, Iman Ibrahim, Alex Mlynarek, Michael Hier, Luiz Paulo Kowalski, Moulay A. Alaoui-Jamali and Sabrina Daniela da Silva _

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Oncotarget. 2017; 8:55511-55524. https://doi.org/10.18632/oncotarget.19224

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Joshua Lubov1, Mariana Maschietto2, Iman Ibrahim1, Alex Mlynarek1, Michael Hier1, Luiz Paulo Kowalski3, Moulay A. Alaoui-Jamali1 and Sabrina Daniela da Silva1

1Department of Otolaryngology Head and Neck Surgery, Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine and Oncology, McGill University, Montreal, QC, Canada

2Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, SP, Brazil

3Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Cancer Center, São Paulo, SP, Brazil

Correspondence to:

Sabrina Daniela da Silva, email: [email protected]

Keywords: miRNAs, prognosis, head and neck cancer, therapeutics

Received: February 09, 2017     Accepted: June 05, 2017     Published: July 13, 2017


Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at advanced stages, incurring significant high mortality and morbidity. This review explored the risk stratification of miRNAs, and investigated the impact of miRNA networking in HNSCC prognostication. We performed a meta-analysis and a systematic literature search on online databases for papers published prior to December 1, 2016. The list of miRNAs was uploaded to MetacoreTM to construct a protein-protein interaction network, which was used to identify targets of the miRNAs and potential drugs. In addition, a representative network was further validated by immunohistochemistry in a cohort of 100 patients. We found 116 studies that included 8,194 subjects, in which the relationship between miRNA expression and prognosis of HNSCC were analyzed. Significant elevated expressions of 27 miRNAs and decreased expression of 26 miRNAs were associated with poor outcome. After excluding the studies causing heterogeneity, a fixed model was applied, which showed a statistically significant association between increased expression of miR-21 and poor survival (Pooled HR = 1.81,95% CI = 0.66–2.95, P < 0.005). We identified four networks affected by the miRNAs expression and enriched in genes related to metabolic processes and regulation of cell mitogenesis in response to extracellular stimuli. One network point out to 16 miRNAs directly or indirectly involved in the regulation of androgen-receptor (AR). Evaluation of AR protein expression in our cohort revealed that patients with upregulation of AR had poor survival rates (log-rank test, P < 0.005). This study showed that miRNAs have potential prognostic value to serve as screening tool for HNSCC during the follow-up. In addition, the implementation of a network-based analysis may reveal proteins with potential to be used as a biomarker.

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