Five miRNAs as novel diagnostic biomarker candidates for primary nasopharyngeal carcinoma.

Jin-Feng Tang,Hai-Li Huang,Jun Cao,Ya-Hong Wang,Tie Liu,Zi-Ying Lin,La-Wei Yang,Hui-Juan He,Gang Liu,Zhong-Hua Yu

doi:10.7314/apjcp.2014.15.18.7575

Abstract

MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR- 183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR- 93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.

Highlights

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia relative to other regions, in the Cantonese region around Guangdong in China (Qiu et al, 2011)
Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. quantitative real-time PCR (qRT-PCR) revealed five differentially expressed miRNAs in nasopharyngeal carcinomas (NPC) tissue samples relative to control samples (p
The down-regulation of tumor suppressor gene expression by microRNAs is increasingly recognized to be an important mechanism of nasopharyngeal tumorigenesis (Li et al, 2014; Ma et al, 2014). miRNAs are endogenous, small non-coding RNA molecules that completely or partially bind to target mRNAs and either block translation or lead to degradation to inhibit gene expression (Li et al, 2011; Marquitz et al, 2012; Liu et al, 2014). miRNAs serve as essential posttranscriptional regulators that can influence cancer development and progression, with aberrant expression patterns observed in multiple cancer types (Marquitz, 2012)

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia relative to other regions, in the Cantonese region around Guangdong in China (Qiu et al, 2011). Due to its unique location and a lack of specific symptoms, NPC is rarely detected during regular medical examinations and is often highly invasive in the late stages (Guo et al, 2013; Liu et al, 2013b). If these patients are diagnosed earlier or if relapses can be predicted sooner, clinical management would be greatly improved (Lin et al, 2014). MiRNAs serve as essential posttranscriptional regulators that can influence cancer development and progression, with aberrant expression patterns observed in multiple cancer types (Marquitz, 2012). Different cancer types, stages and differentiation grades may have unique miRNA expression signatures, enabling the use of miRNAs as biomarkers for cancer

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Results

Conclusion