背景:胰腺癌(PaCa)是最棘手和最致命的恶性肿瘤之一,与长链非编码RNA(lncRNAs)的失调有关,它们是一大类大于200nt的非编码RNA,充当竞争内源性RNA或海绵,以诱导肿瘤生物学行为。然而,它们在治疗胰腺癌中的临床价值解释不清,但它们对于改善PaCa患者的预后至关重要。
方法:我们通过使用全转录组测序分析分析了PaCa患者的血浆来源的外泌体lncRNA谱,并鉴定了显着差异表达的lncRNA,包括LINC01268、LINC02802、AC124854.1和AL132657.1。在目前的研究中,通过定量实时聚合酶链反应(qRT^PCR)验证了PaCa血浆中4种血浆来源的外泌体lncRNA的表达水平.还评估了四种lncRNAs的表达与PaCa患者的临床病理特征之间的关系。
结果:我们证明,与正常对照组相比,外泌体LINC01268,LINC02802,AC124854.1和AL132657.1在PaCa血浆中高表达;此外,它们与糖抗原19-9(CA19-9)的血清表达呈正相关。4种lncRNAs的接受者工作特征曲线(AUC)分别为0.8421、0.6544、0.7190和0.6321,4种外泌体lncRNAs组合的AUC值增加至0.8476,灵敏度为0.72,特异性为0.89。这些结果表明,血浆来源的外泌体基因LINC01268,LINC02802,AC124854.1和AL132657.1可能是PaCa的新型诊断标志物。
结论:我们的研究表明,PaCa患者的血浆来源的外泌体lncRNAs是新的基于血液的疾病生物标志物。
BACKGROUND: Pancreatic cancer (PaCa) is one of the most intractable and fatal malignancies and is associated with the dysregulation of long noncoding RNAs (lncRNAs), which are a large class of noncoding RNAs larger than 200 nt that act as competing endogenous RNAs or sponges for miRNAs to induce tumour biological behaviours. However, their clinical value in treating pancreatic cancer has been poorly explained, but they are essential for improving the prognosis of PaCa patients.
METHODS: We analysed the plasma-derived exosomal lncRNA profiles of PaCa patients by using whole-transcriptome sequencing analysis and identified significantly differentially expressed lncRNAs, including LINC01268, LINC02802, AC124854.1, and AL132657.1. In the current study, the expression levels of four plasma-derived exosomal lncRNAs in PaCa plasma were validated via quantitative real-time polymerase chain reaction (qRT‒PCR). The relationship between the expression of the four lncRNAs and the clinicopathological features of patients with PaCa was also evaluated.
RESULTS: We demonstrated that exosomal LINC01268, LINC02802, AC124854.1 and AL132657.1 were highly expressed in PaCa plasma compared with those in normal controls; moreover, they were positively correlated with the serum expression of carbohydrate antigen 19-9 (CA19-9). The receiver operating characteristic curves (AUCs) of the four lncRNAs were 0.8421, 0.6544, 0.7190, and 0.6321, and the AUC value of the combination of the four exosomal lncRNAs increased to 0.8476, with a sensitivity of 0.72 and specificity of 0.89. These results suggested that the plasma-derived exosomal genes LINC01268, LINC02802, AC124854.1, and AL132657.1 may be novel diagnostic markers for PaCa.
CONCLUSIONS: Our research demonstrated that the plasma-derived exosomal lncRNAs of PaCa patients are novel blood-based biomarkers of disease.