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Abstract：
BACKGROUND: 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.
METHODS: 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-ΔΔCt method. When the p-value was less than 0.05, the differences were considered statistically significant.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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-ΔΔCt method. When the p-value was less than 0.05, the differences were considered statistically significant.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：耐药性的发展和高死亡率是非小细胞肺癌（NSCLC）中观察到的主要问题。因此,高度需要指示和预测朝向这些不利方向的疾病发展的生物标志物。许多研究表明，miRNA表达的变化可能与治疗反应和疾病预后有关。因此表明其具有广泛的临床应用的潜在生物标志物价值。本研究的目的是研究miR-181a-5p的表达水平。miR-630及其在NSCLC肿瘤组织和血浆样本中的靶标；并分析其与NSCLC患者对治疗的反应和疾病预后的关系。
方法：该研究是在美国国家癌症研究所胸外科和肿瘤科接受手术治疗的NSCLC患者中获得的89个配对组织样本和血浆样本中进行的。使用TaqManmiRNA特异性引物通过qRT-PCR进行miR-181a-5p和miR-630表达的分析。而BCL2，LMO3，PTEN，SNAI2、WIF1表达水平用KAPASYBRFASTqPCR试剂盒鉴定。每个样品一式三份检查并按照2-ΔΔCt方法计算。当p值小于0.05时,认为差异具有统计学意义。
结果：发现与对照样品相比，NSCLC组织和血浆样品中的miR-181a-5p和miR-630表达水平显着降低。此外，miR-181a-5p在肿瘤组织和血浆中低表达的患者比miRNA高表达的患者具有更长的PFS率.肿瘤中miR-630表达降低与NSCLC患者更好的OS显著相关。此外,miR-181a-5p的表达，以及肿瘤组织中的miR-630，是NSCLC患者OS的统计学显著变量。此外，在NSCLC患者血浆样本中,循环miR-181a-5p可被评估为OS和PFS的显著独立预后因素.
结论：我们的发现表明miR-181a-5p和miR-630表达水平具有预测和预测的潜力，因此可以改善NSCLC患者的个体化治疗和预后。循环miR-181a-5p作为NSCLC的非侵入性生物标志物具有潜在的临床价值。
方法：该研究是在美国国家癌症研究所胸外科和肿瘤科接受手术治疗的NSCLC患者中获得的89个配对组织样本和血浆样本中进行的。使用TaqManmiRNA特异性引物通过qRT-PCR进行miR-181a-5p和miR-630表达的分析。而BCL2，LMO3，PTEN，SNAI2、WIF1表达水平用KAPASYBRFASTqPCR试剂盒鉴定。每个样品一式三份检查并按照2-ΔΔCt方法计算。当p值小于0.05时,认为差异具有统计学意义。
结果：发现与对照样品相比，NSCLC组织和血浆样品中的miR-181a-5p和miR-630表达水平显着降低。此外，miR-181a-5p在肿瘤组织和血浆中低表达的患者比miRNA高表达的患者具有更长的PFS率.肿瘤中miR-630表达降低与NSCLC患者更好的OS显著相关。此外,miR-181a-5p的表达，以及肿瘤组织中的miR-630，是NSCLC患者OS的统计学显著变量。此外，在NSCLC患者血浆样本中,循环miR-181a-5p可被评估为OS和PFS的显著独立预后因素.
结论：我们的发现表明miR-181a-5p和miR-630表达水平具有预测和预测的潜力，因此可以改善NSCLC患者的个体化治疗和预后。循环miR-181a-5p作为NSCLC的非侵入性生物标志物具有潜在的临床价值。
