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胰腺癌患者血浆衍生的外泌体长非编码 RNA 作为疾病新型的基于血液的生物标志物。

Plasma-derived exosomal long noncoding RNAs of pancreatic cancer patients as novel blood-based biomarkers of disease.

机构信息

Central Laboratory, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, 361015, China.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.

出版信息

BMC Cancer. 2024 Aug 6;24(1):961. doi: 10.1186/s12885-024-12755-z.

Abstract

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.

摘要

背景

胰腺癌(PaCa)是一种最棘手和致命的恶性肿瘤,与长链非编码 RNA(lncRNA)的失调有关,lncRNA 是一类大于 200nt 的非编码 RNA,作为竞争内源性 RNA 或 miRNA 的海绵,诱导肿瘤的生物学行为。然而,它们在治疗胰腺癌中的临床价值尚未得到充分解释,但对于改善 PaCa 患者的预后至关重要。

方法

我们通过全转录组测序分析分析了胰腺癌患者的血浆衍生外泌体 lncRNA 谱,并鉴定出了差异表达的 lncRNA,包括 LINC01268、LINC02802、AC124854.1 和 AL132657.1。在本研究中,通过定量实时聚合酶链反应(qRT-PCR)验证了 4 种血浆衍生外泌体 lncRNA 在 PaCa 血浆中的表达水平。还评估了这四种 lncRNA 的表达与 PaCa 患者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,它们与血清碳水化合物抗原 19-9(CA19-9)的表达呈正相关。这四种 lncRNA 的受试者工作特征曲线(AUCs)分别为 0.8421、0.6544、0.7190 和 0.6321,四种外泌体 lncRNA 组合的 AUC 值增加到 0.8476,敏感性为 0.72,特异性为 0.89。这些结果表明,源自血浆的外泌体基因 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,胰腺癌患者的血浆衍生外泌体 lncRNA 是一种新的疾病血液生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cce/11301836/53edc6ddce3d/12885_2024_12755_Fig1_HTML.jpg

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