Abstract
BackgroundEarly diagnosis is critical to reduce the mortality caused by nasopharyngeal carcinoma (NPC). MicroRNAs (miRNAs) are dysregulated and play important roles in carcinogenesis. Therefore, this study aimed to identify diagnostically relevant circulating miRNA signatures in patients with NPC.MethodsTotal RNA was extracted from whole blood samples obtained from 120 patients with NPC, 30 patients with head-neck tumors (HNT), and 30 healthy subjects (HSs), and examined by using a custom microarray. The expression levels of four miRNAs identified by using the microarray were validated with quantitative real-time reverse transcription polymerase chain reaction. The 120 patients with NPC and 30 HSs were randomly assigned to training group-1 and validation group-1, respectively. By using significance analysis of microarray (SAM), the specific miRNA expression profiles in whole blood from patients with NPC are obtained. By using lasso regression and adaptive boosting, a diagnostic signature was identified in training group-1, and its accuracy was verified in validation group-1. By using the same methods, another signature to distinguish patients with NPC from those with HNT and HSs was identified in training group-2 and confirmed in validation group-2.ResultsThere were 117 differentially expressed miRNAs (upregulated and downregulated fold change ≥ 1.5) between the patients with NPC and HSs, among which an 8-miRNA signature was identified with 96.43% sensitivity and 100% specificity [area under the curve (AUC) = 0.995] to diagnose NPC in training group-1 and 86.11% sensitivity and 88.89% specificity (AUC = 0.941) in validation group-1. Compared with traditional Epstein–Barr virus (EBV) seromarkers, this signature was more specific for NPC. Furthermore, a 16-miRNA signature to differentiate NPC from HNT and HS (HNT-HS) was established from 164 differentially expressed miRNAs, which diagnosed NPC and HNT-HS with 100% accuracy (AUC = 1.000) in training group-2 and 87.04% (AUC = 0.924) in validation group-2.ConclusionsThe present study identified two miRNA signatures for the highly accurate diagnosis and differential diagnosis of patients with NPC from HSs and patients with HNT. The identified miRNAs might represent novel serological biomarkers and potential therapeutic targets for NPC.
Highlights
Diagnosis is critical to reduce the mortality caused by nasopharyngeal carcinoma (NPC)
According to the global cancer statistics reported by the International Agency for Research on Cancer, over 84,000 new nasopharyngeal carcinoma (NPC) cases are diagnosed per year, of which more than 80% occur in Asia and 5% in Europe [1]
The Micro‐ RNAs (miRNAs) expression profiles of whole blood in patients with NPC and those with head-neck tumors (HNT) As far as we know, there have been no reports on miRNA expression profiles of whole blood in patients with NPC
Summary
Diagnosis is critical to reduce the mortality caused by nasopharyngeal carcinoma (NPC). If patients are diagnosed at an early stage, such as stage I, they only need to receive simple radiation treatment and have a very good prognosis, with few adverse reactions to the therapy. This clearly indicates that early diagnosis is critical to improve the survival and life quality of patients with NPC. As NPC is asymptomatic or has non-specific symptoms at the early stage, more than 80% of patients with NPC are first diagnosed at a late stage (III or IV), often with cervical lymph node metastasis [7], which leads to reduced survival. Early diagnosis of NPC is a significant clinical challenge
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