Identification of Circulating miR-762 as a Novel Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer

Technol Cancer Res Treat. 2020 Jan-Dec:19:1533033820964222. doi: 10.1177/1533033820964222.

Abstract

Background: MicroRNAs (miRNAs) have been demonstrated to play critical roles in tumorigenesis of non-small cell lung cancer (NSCLC), and circulating miRNAs are a valuable source of biomarkers for the clinical management of NSCLC. The aim of this study was to determine the value of serum miR-762 as a diagnostic and prognostic biomarker for NSCLC.

Methods: We examined circulating miR-762 expression in 148 NSCLC patients and 60 healthy individuals using the quantitative real-time polymerase chain reaction (qRT-PCR). The effect of miR-762 downregulation on the proliferative capacity of NSCLC cells were also explored.

Results: The serum miR-762 levels were significantly upregulated in NSCLC patients compared to the healthy individuals. Receiver operating characteristics (ROC) curve analysis revealed that circulating miR-762, carcinoembryonic antigen (CEA), CYFRA21-1 and a combination of these 3 biomarkers yield the areas under the curve (AUC) of 0.874, 0.826, 0.41 and 0.969, respectively. Interestingly, circulating miR-762 identified the NSCLC patients at the clinical stage I from healthy controls with an AUC value of 0.920. In addition, serum miR-762 expression was significantly correlated with clinical stage, lymph node metastasis, histological grade and gefitinib-resistance. The survival analysis showed that NSCLC patients in the high serum miR-762 group suffered worse overall survival and relapse-free survival than those in the low serum miR-762 group. The multivariate Cox proportional hazards regression analysis revealed high circulating miR-762 was an independent unfavorable prognostic factor. Downregulation of miR-762 significantly suppressed the proliferative capacity of NSCLC cells in vitro, and bioinformatic analysis of the potential downstream targets of miR-762 identified many important cancer-associated pathways.

Conclusions: In conclusion, serum miR-762 might serve as a promising diagnostic and prognostic biomarker for the NSCLC.

Keywords: biomarker; diagnosis; non-small cell lung cancer; prognosis; serum miR-762.

MeSH terms

  • Antigens, Neoplasm / blood*
  • Biomarkers, Tumor / blood
  • Carcinoembryonic Antigen / blood*
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / genetics
  • Drug Resistance, Neoplasm
  • Female
  • Gefitinib / administration & dosage
  • Gefitinib / adverse effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Keratin-19 / blood*
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Neoplastic Cells, Circulating / metabolism
  • Prognosis

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • Keratin-19
  • MIRN762 microRNA, human
  • MicroRNAs
  • antigen CYFRA21.1
  • Gefitinib