Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11835, Egypt.
Department of Medical Oncology, National Cancer Institute, NCI, Cairo University, Cairo, Egypt.
Sci Rep. 2024 Feb 27;14(1):4823. doi: 10.1038/s41598-024-55083-9.
Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30-40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.
长链非编码 RNA 已被证明参与了许多生理和病理途径。迄今为止,恶性胸膜间皮瘤 (MPM) 被认为是一种极具侵袭性的癌症。造成这种情况的一个原因是疾病的晚期诊断,这种情况可能在接触石棉后 30-40 年内发生。除了活检等侵入性方法外,迫切需要开发新的、敏感的、廉价的和易于使用的方法来早期检测这种疾病。本研究旨在确定间皮瘤患者血浆中循环 lncRNA 的表达,以鉴定潜在的生物标志物。选择了之前在间皮瘤组织中显示异常表达的 10 个长链非编码 RNA 作为后续验证的候选物。通过定量 PCR (qPCR) 验证了这 10 个候选长链非编码 RNA 在间皮瘤患者与健康对照者的人血浆样本中的表达。与对照组相比,患者血浆样本中循环 GAS5、SNHG8 和 MALAT1 的表达水平明显更高。MALAT1 和 SNHG8 的 ROC 分析显示出 88.89%的灵敏度和 66.67%的特异性。这些标志物的灵敏度大于 GAS5(灵敏度 72.22%和特异性 66.67%)。GAS5 的回归模型具有统计学意义,而 SNHG8 和 MALAT1 的回归模型则由于样本量小而不具有统计学意义。三条 ROC 曲线的 AUC 可接受且显著:GAS5 为 0.7519,SNHG8 为 0.7352,MALAT1 为 0.7185。这一发现证实了它们作为标志物的能力。这三个长链非编码 RNA 不受年龄、性别或吸烟状况的影响。这三个长链非编码 RNA 具有作为独立预测诊断生物标志物的巨大潜力。尽管 MALAT1 的预测模型没有显著差异,但 MALAT1在患者中的表达明显高于对照组(p=0.0266),记录的灵敏度和特异性大于 GAS5。