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

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.

Automated summary

This study aimed to investigate the potential risk of circulating HPV-DNA in NSCLC and analyze the abnormally expressed miRNAs in circulating HPV-DNA-positive NSCLC. Circulating HPV-DNA was found in 16 NSCLC patients, with higher levels of miR-183, miR-210, and miR-182, and lower levels of miR-144 compared to HPV-DNA-negative patients. Using miR-210 had the highest AUC for identifying circulating HPV-DNA-positive NSCLC patients, and the combination of miR-210 and miR-144 showed the best predictive performance. These findings suggest that circulating HPV-DNA could be a risk factor in NSCLC, and plasma miR-183, miR-210, miR-182, and miR-144 can be reliable biomarkers for identifying circulating HPV-DNA-positive NSCLC.