Department of Clinical Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
Cancer Biol Ther. 2021 Feb 1;22(2):136-148. doi: 10.1080/15384047.2021.1872155. Epub 2021 Feb 4.
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.
本研究旨在确定循环 HPV-DNA 在非小细胞肺癌（NSCLC）中的潜在风险，并分析循环 HPV-DNA 阳性 NSCLC 中异常表达的 miRNA。采用 HPV 通用引物检测 100 例 NSCLC 患者外周血中 HPV-DNA 的存在。分析循环-HPV-DNA 与 NSCLC 患者特征之间的关系。然后，基于 TCGA 数据库筛选出 NSCLC 中 8 个差异表达的 miRNA。采用实时定量 PCR 检测循环 HPV-DNA 阳性 NSCLC 患者 miRNA 的水平。绘制 ROC 曲线评估诊断性能。在 16 例患者中发现了循环 HPV-DNA。HPV-DNA 阳性患者中低分化 NSCLC、晚期肺癌和淋巴结转移的比例高于 HPV-DNA 阴性患者。与 HPV-DNA 阴性 NSCLC 患者相比，HPV-DNA 阳性 NSCLC 患者的 miR-183、miR-210 和 miR-182 水平显著升高，miR-144 水平显著降低。当使用单个 miRNA 来识别循环 HPV-DNA 阳性 NSCLC 患者时，miR-210 的 ROC 曲线下面积（AUC）高于其他 miRNA，且其敏感性和特异性也更高。此外，两个 miRNA 的联合比单个 miRNA 更有效。其中，miR-210+miR-144 具有最高的 AUC 值，表现出最佳的预测性能。循环 HPV-DNA 可能是 NSCLC 的一个危险因素。血浆 miR-183、miR-210、miR-182 和 miR-144 可作为识别循环 HPV-DNA 阳性 NSCLC 的可靠生物标志物。
