Biomarkers and Experimental Therapeutics in Cancer, IdiPAZ, 28046 Madrid, Spain.
Medical Oncology Department, La Paz University Hospital, 28046 Madrid, Spain.
Int J Mol Sci. 2023 Jul 14;24(14):11464. doi: 10.3390/ijms241411464.
Despite advances in non-small cell lung cancer (NSCLC) research, this is still the most common cancer type that has been diagnosed up to date. microRNAs have emerged as useful clinical biomarkers in both tissue and liquid biopsy. However, there are no reliable predictive biomarkers for clinical use. We evaluated the preclinical use of seven candidate miRNAs previously identified by our group. We collected a total of 120 prospective samples from 88 NSCLC patients. miRNA levels were analyzed via qRT-PCR from tissue and blood samples. miR-124 gene target prediction was performed using RNA sequencing data from our group and interrogating data from 2952 NSCLC patients from two public databases. We found higher levels of all seven miRNAs in tissue compared to plasma samples, except for miR-124. Our findings indicate that levels of miR-124, both free-circulating and within exosomes, are increased throughout the progression of the disease, suggesting its potential as a marker of disease progression in both advanced and early stages. Our bioinformatics approach identified KPNA4 and SPOCK1 as potential miR-124 targets in NSCLC. miR-124 levels can be used to identify early-stage NSCLC patients at higher risk of relapse.
尽管非小细胞肺癌(NSCLC)的研究取得了进展,但这仍然是迄今为止诊断最常见的癌症类型。 microRNAs 已成为组织和液体活检中有用的临床生物标志物。 然而,目前还没有可靠的用于临床的预测生物标志物。 我们评估了我们小组先前鉴定的七种候选 miRNA 的临床前用途。 我们从 88 名 NSCLC 患者中总共收集了 120 份前瞻性样本。 通过 qRT-PCR 从组织和血液样本中分析 miRNA 水平。 使用我们小组的 RNA 测序数据和来自两个公共数据库的 2952 名 NSCLC 患者的数据进行 miR-124 基因靶标预测。 我们发现所有七种 miRNA 的组织水平均高于血浆样本,除了 miR-124。 我们的研究结果表明,miR-124 的水平,无论是游离循环还是外泌体中的,在整个疾病进展过程中都会增加,表明其在晚期和早期阶段都有作为疾病进展标志物的潜力。 我们的生物信息学方法鉴定出 KPNA4 和 SPOCK1 是 NSCLC 中潜在的 miR-124 靶标。 miR-124 水平可用于识别复发风险较高的早期 NSCLC 患者。