National Cancer Institute, Vilnius, 08406, Lithuania.
Vilnius University Life Sciences Center, Vilnius, 10223, Lithuania.
BMC Cancer. 2023 Sep 12;23(1):857. doi: 10.1186/s12885-023-11365-5.
The development of drug resistance and high mortality rates are the major problems observed in non-small cell lung cancer (NSCLC). Biomarkers indicating and predicting disease development towards these unfavorable directions are therefore on high demand. Many studies have demonstrated that changes in miRNAs expression may be associated with a response to treatment and disease prognosis, thus suggesting its potential biomarker value for a broad spectrum of clinical applications. The aim of the present study was to investigate the expression level of miR-181a-5p, miR-630, and its targets in NSCLC tumor tissue and plasma samples; and to analyze its association with NSCLC patient's response to treatment and disease prognosis.
The study was performed in 89 paired tissue specimens and plasma samples obtained from NSCLC patients who underwent surgical treatment at the Department of Thoracic Surgery and Oncology of the National Cancer Institute. Analysis of miR-181a-5p and miR-630 expression was performed by qRT-PCR using TaqMan miRNA specific primers. Whereas BCL2, LMO3, PTEN, SNAI2, WIF1 expression levels were identified with KAPA SYBR FAST qPCR Kit. Each sample was examined in triplicate and calculated following the 2-t method. When the p-value was less than 0.05, the differences were considered statistically significant.
It was found that miR-181a-5p and miR-630 expression levels in NSCLC tissue and plasma samples were significantly decreased compared with control samples. Moreover, patients with low miR-181a-5p expression in tumor tissue and plasma had longer PFS rates than those with high miRNA expression. Decreased miR-630 expression in tumor was statistically significantly associated with better NSCLC patients' OS. In addition, the expression of miR-181a-5p, as well as miR-630 in tumor tissue, are the statistically significant variables for NSCLC patients' OS. Moreover, in NSCLC patient plasma samples circulating miR-181a-5p can be evaluated as significant independent prognostic factors for OS and PFS.
Our findings indicate the miR-181a-5p and miR-630 expression levels have the potential to prognose and predict and therefore improve the treatment individualization and the outcome of NSCLC patients. Circulating miR-181a-5p has the potential clinical value as a non-invasive biomarker for NSCLC.
耐药性的发展和高死亡率是非小细胞肺癌（NSCLC）的主要问题。因此，能够指示和预测疾病向这些不利方向发展的生物标志物需求量很大。许多研究表明，miRNA 表达的变化可能与治疗反应和疾病预后相关，这表明其具有广泛的临床应用的潜在生物标志物价值。本研究旨在研究 NSCLC 肿瘤组织和血浆样本中 miR-181a-5p、miR-630 及其靶标的表达水平；并分析其与 NSCLC 患者对治疗的反应和疾病预后的关系。
本研究在国家癌症研究所胸外科和肿瘤学系接受手术治疗的 89 对 NSCLC 患者的组织标本和血浆样本中进行。使用 TaqMan miRNA 特异性引物通过 qRT-PCR 分析 miR-181a-5p 和 miR-630 的表达。使用 KAPA SYBR FAST qPCR 试剂盒鉴定 BCL2、LMO3、PTEN、SNAI2、WIF1 的表达水平。每个样本一式三份进行检查，并根据 2-t 法计算。当 p 值小于 0.05 时，差异被认为具有统计学意义。
发现与对照样本相比，NSCLC 组织和血浆样本中的 miR-181a-5p 和 miR-630 表达水平显著降低。此外，肿瘤组织和血浆中 miR-181a-5p 低表达的患者 PFS 率高于 miRNA 高表达的患者。肿瘤中 miR-630 表达的降低与 NSCLC 患者 OS 的改善具有统计学意义。此外，miR-181a-5p 和肿瘤组织中 miR-630 的表达是 NSCLC 患者 OS 的统计学显著变量。此外，在 NSCLC 患者的血浆样本中，循环 miR-181a-5p 可作为 OS 和 PFS 的独立预后因素。
我们的研究结果表明，miR-181a-5p 和 miR-630 的表达水平具有预测和预后的潜力，从而能够改善 NSCLC 患者的个体化治疗和结局。循环 miR-181a-5p 具有作为 NSCLC 非侵入性生物标志物的潜在临床价值。
