Department of Internal Medicine, Dermatology and Psychiatry, Universidad de La Laguna, 38071 San Cristóbal de La Laguna, Spain.
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, 38296 San Cristóbal de La Laguna, Spain.
Int J Mol Sci. 2023 Aug 4;24(15):12437. doi: 10.3390/ijms241512437.
Lung cancer (LC) is the most common cause of cancer death, with 75% of cases being diagnosed in late stages. This study aimed to determine potential miRNAs as biomarkers for the early detection of LC in chronic obstructive pulmonary disease (COPD) cases. Ninety-nine patients were included, with registered clinical and lung function parameters followed for 6 years. miRNAs were determined in 16 serum samples from COPD patients (four with LC and four controls) by next generation sequencing (NGS) at LC diagnosis and 3 years before. The validation by qPCR was performed in 33 COPD-LC patients and 66 controls at the two time points. Over 170 miRNAs (≥10 TPM) were identified; among these, miR-224-5p, miR-206, miR-194-5p, and miR-1246 were significantly dysregulated ( < 0.001) in COPD-LC 3 years before LC diagnosis when compared to the controls. The validation showed that miR-1246 and miR-206 were differentially expressed in COPD patients who developed LC three years before ( = 0.035 and = 0.028, respectively). The in silico enrichment analysis showed miR-1246 and miR-206 to be linked to gene mediators in various signaling pathways related to cancer. Our study demonstrated that miR-1246 and miR-206 have potential value as non-invasive biomarkers of early LC detection in COPD patients who could benefit from screening programs.
肺癌(LC)是癌症死亡的最常见原因,其中 75%的病例在晚期诊断。本研究旨在确定潜在的 miRNA 作为 COPD 患者 LC 早期检测的生物标志物。共纳入 99 例患者,记录其临床和肺功能参数,随访 6 年。在 LC 诊断和 3 年前,通过下一代测序(NGS)在 16 例 COPD 患者(4 例 LC 和 4 例对照)的 16 份血清样本中测定 miRNA。在两个时间点,通过 qPCR 在 33 例 COPD-LC 患者和 66 例对照中进行验证。鉴定出超过 170 种 miRNA(≥10 TPM);其中,miR-224-5p、miR-206、miR-194-5p 和 miR-1246 在 COPD-LC 患者中明显失调(<0.001),与对照组相比,在 LC 诊断前 3 年。验证显示,miR-1246 和 miR-206 在 COPD 患者中表达不同,这些患者在 LC 前三年发展为 LC(=0.035 和=0.028)。基于网络的富集分析表明,miR-1246 和 miR-206 与各种与癌症相关的信号通路中的基因介质有关。我们的研究表明,miR-1246 和 miR-206 具有作为 COPD 患者早期 LC 检测的非侵入性生物标志物的潜在价值,这些患者可能受益于筛查计划。