ArticlesPrognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis
Introduction
According to the International Agency for Research on Cancer, 84 400 incident cases of nasopharyngeal carcinoma and 51 600 disease-related deaths occurred in 2008.1 The highest prevalence (20–50 cases per 100 000 individuals) of this cancer occurred in south China whereas the lowest prevalence (0·5 cases per 100 000 individuals) was reported in white populations in Europe and the USA.2
The TNM staging system provides a useful benchmark for prognostic definition and establishment of treatment strategy. According to the US National Comprehensive Cancer Network guidelines, patients with early-stage nasopharyngeal carcinoma should be treated with radiotherapy, whereas patients with advanced disease should receive chemoradiotherapy. However, large variations in the clinical outcomes are reported in patients with the same stage and similar treatment regimens.3 These findings suggest that the present staging system is inadequate for definition of prognosis and does not reflect the biological heterogeneity of cancer because it classifies the extent of disease chiefly on the basis of anatomical information. With the rapid advance in understanding of the molecular biology of nasopharyngeal carcinoma, various biomarkers that associate with prognosis or efficacy of treatment have been reported, including Epstein-Barr virus (EBV) DNA, lactate dehydrogenase, and VEGF.4, 5, 6 Nevertheless, more studies are required to confirm their clinical roles and new prognostic biomarkers are needed for this disease.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate various biological processes post-transcriptionally and are dysregulated in most cancer types.7, 8 miRNAs have been reported in the development and progression of many cancers9, 10, 11, 12, 13, 14, 15 and are potential biomarkers for cancer diagnosis, prognosis, and personalised therapy.16 miRNAs were reported to be expressed aberrantly in nasopharyngeal carcinoma tissues compared with normal epithelial tissue, and promote an aggressive tumour phenotype by changing the expression of their mRNA targets.17, 18 The clinical significance of miRNAs in nasopharyngeal carcinoma, however, has not been established.
We aimed to examine the miRNA expression profiles in tissue samples of nasopharyngeal carcinoma to explore their clinical significance in disease development and progression, and provide information for personalised therapy.
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Clinical specimens and study design
We obtained 465 pathologically proven and non-distant-metastatic paraffin-embedded nasopharyngeal carcinoma specimens for this study. 312 specimens were obtained from the Sun Yat-sen University Cancer Center (Guangzhou, China) between Jan 16, 2003, and Feb 25, 2006, and 153 were collected from the West China Hospital of Sichuan University (Chengdu, China) between April 1, 2002, and May 22, 2008. We also acquired 18 paraffin-embedded non-cancer nasopharyngitis biopsy samples from patients who
Results
465 nasopharyngeal carcinoma specimens were obtained for this study. Table 1 lists the clinical characteristics of patients with nasopharyngeal carcinoma in the training, internal validation, and independent sets. On microarray analysis, 41 miRNAs were differentially expressed between 312 samples of nasopharyngeal carcinoma from the combined training and internal validation sets and 18 non-cancer nasopharyngitis samples (fold change ≥2·5, false discovery rate 0; appendix pp 2–3). For this 41
Discussion
Prognostic assessment is crucial for formation of appropriate treatment choices. In routine clinical practice, the TNM staging system is the key prognostic determinant for patients with nasopharyngeal carcinoma. However, large variations in the clinical outcomes of patients with the same cancer stage have been reported, suggesting that the present staging system is not adequate for prognosis. We developed a five-miRNA signature that was predictive of survival of patients with nasopharyngeal
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