Evaluation of microRNAs as potential biomarkers in circulating HPV-DNA-positive non-small cell lung cancer patients

Cancer Biol Ther. 2021 Feb 1;22(2):136-148. doi: 10.1080/15384047.2021.1872155. Epub 2021 Feb 4.

Abstract

The aim of the present study was to identify the potential risk of circulating-HPV-DNA in non-small cell lung cancer (NSCLC) and to analyze abnormally expressed miRNAs in circulating HPV-DNA-positive NSCLC. HPV universal primers were used to detect the presence of HPV-DNA in the peripheral blood of 100 patients with NSCLC. The relationship between circulating-HPV-DNA and NSCLC patients characteristics was analyzed. Then, eight differentially expressed miRNAs in NSCLC were screened based on the TCGA database. The levels of miRNAs in circulating HPV-DNA-positive NSCLC patients were detected by real-time quantitative PCR. ROC curves were generated to evaluate the diagnostic performance. Circulating-HPV-DNA was found in 16 patients. The proportion of HPV-DNA-positive patients with poorly differentiated NSCLC, advanced lung cancer and lymph node metastasis was higher than that of HPV-DNA-negative patients. The levels of miR-183, miR-210 and miR-182 were significantly higher and miR-144 was significantly lower in HPV-DNA-positive NSCLC than those in HPV-DNA-negative NSCLC patients. When using a single miRNA to identify circulating HPV-DNA-positive NSCLC patients, miR-210 had a higher area under the ROC curve (AUC) than other miRNAs, and its sensitivity and specificity were also higher. In addition, the combination of two miRNAs was more effective than a single miRNA. Among them, miR-210+ miR-144 had the highest AUC value and showed the best prediction performance. Circulating-HPV-DNA may serve as a risk factor in NSCLC. Plasma miR-183, miR-210, miR-182 and miR-144 can be used as reliable biomarkers to identify circulating HPV-DNA-positive NSCLC.

Keywords: HPV-DNA; TCGA database; diagnosis; microRNA; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell-Free Nucleic Acids / genetics*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • MicroRNAs / metabolism*
  • Papillomavirus Infections / genetics*
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • MicroRNAs

Grants and funding

The present study was supported by the Zhenjiang Social Development Project [SH2017024] and the Jiangsu Province 2018 Preventive Medicine Research Project [Y2018108].