Genome-wide study of salivary microRNAs as potential noninvasive biomarkers for detection of nasopharyngeal carcinoma

BMC Cancer. 2019 Aug 28;19(1):843. doi: 10.1186/s12885-019-6037-y.

Abstract

Background: Recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis have opened a new field of utilizing circulating miRNAs as cancer biomarkers. In this pilot study, we conducted for the first time, to our knowledge, the evaluation of the applicability of salivary miRNAs as novel biomarkers for nasopharyngeal carcinoma (NPC) detection.

Methods: Microarray miRNA expression profiling was performed on saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls, and 12 significantly down-regulated miRNAs were selected for quantitative real-time-PCR (qRT-PCR) validation and further analysis. Their target genes enriched by gene ontology and pathway analysis were used to construct regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy.

Results: Twelve dysregulated miRNAs screened by microarray that showed the same expression patterns with qRT-PCR analysis. Through bioinformatics analysis, the most prominent hub gene probably regulated by the 12 down-regulated miRNAs is found to be TP53. The ROC including the 12 miRNAs separated NPC patients from healthy controls with very high accuracy (areas under the receiver operating characteristic curve [AUC] = 0.999, sensitivity = 100.00%, specificity = 96.00%). Furthermore, if only six significantly dysregulated miRNAs were selected for the ROC analysis, the accuracy is still impressive (AUC = 0.941, sensitivity = 95.45%, specificity = 80.00%).

Conclusions: This study highlights the potential for salivary miRNAs as biomarkers for the detection of NPC. Meanwhile, differentially expressed miRNAs in saliva might play critical roles in NPC by regulating their target genes, which associated with some significant pathways, such as p53 signaling pathway.

Keywords: Biomarkers; MicroRNA; Nasopharyngeal carcinoma; Saliva.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Case-Control Studies
  • Circulating MicroRNA*
  • Computational Biology / methods
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Genome-Wide Association Study
  • Humans
  • Liquid Biopsy
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Nasopharyngeal Carcinoma / diagnosis*
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / metabolism
  • ROC Curve
  • Saliva / metabolism*

Substances

  • Biomarkers, Tumor
  • Circulating MicroRNA
  • MicroRNAs