Identification of two microRNA signatures in whole blood as novel biomarkers for diagnosis of nasopharyngeal carcinoma

Abstract

Background Early 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. Methods Total 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. Results There 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. Conclusions The 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. Electronic supplementary material The online version of this article (10.1186/s12967-019-1923-2) contains supplementary material, which is available to authorized users.

Research status and prospects of biomarkers for nasopharyngeal carcinoma in the era of high‑throughput omics (Review)

“…Therefore, studies into miRNAs have gained a leading position in the field of transcriptomics in recent years (73). Recently, several miRNAs with good diagnostic ability have been found using PCR or microarray technology (76)(77)(78)(79)(80)(81)(82)(83). Two types of EBV-encoded miRNAs, miR-BamHI A rightward transcripts (BART)7-3p and miR-BART13-3p, showed a remarkable potential for the early diagnosis of NPC (76).…”

Circulating Non-Coding RNAs in Head and Neck Cancer: Roles in Diagnosis, Prognosis, and Therapy Monitoring

“…In addition to evaluating EBV-miRNA expression, Wen and colleagues [ 55 ] have undertaken a broad microarray-based screening project using whole blood from cancer-free controls and patients with different HNC subtype diagnoses. They distilled an 8-miRNA signature that distinguishes patients with NPC from healthy controls (HCs) with a 97.14% accuracy (sensitivity, 96.43%; specificity, 100%) and an AUC of 0.995 ( p 0.001).…”

“… Condensed overview of circulating non-coding RNAs with purported diagnostic, prognostic, or treatment response prediction value in HNC [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. …”

MicroRNAs as Therapeutic Targets in Nasopharyngeal Carcinoma

“…A four-miRNA signature of miR-22, miR-572, miR-638, and miR-1234 were identified to be prognostic biomarkers of NPC to the TNM staging system (83). Recently, a 8-miRNA signature including miR-188-5p, miR-1908, miR-3196, miR-3935, miR-4284, miR-4433-5p, miR-4665-3p, miR-513b, and 16-miRNA signature including miR-1224-3p, miR-1280, miR-155-5p, miR-1908, miR-1973, miR-296-5p, miR-361-3p, miR-425-5p, miR-4284, miR-4436b-5p, miR-4439, miR-4665-3p, miR-4706, miR-4740-3p, miR-5091, miR-513b are promising biomarkers for NPC diagnosis (84). Taker together, miRNAs can be as both single biomarkers and signatures for NPC detection, diagnosis, and prognosis (Table 2).…”