Jin Jie, Qin Junjuan, Qi Xuejiao, Zhang Jiasi, Zhang YingLu
Xiong'an Xuanwu Hospital, Baoding, 070001, PR China.
Key Laboratory of Clinical Neurology Ministry of Education, Shijiazhuang, 050000, PR China.
J Neurooncol. 2025 Jun;173(2):419-428. doi: 10.1007/s11060-025-04999-x. Epub 2025 Mar 13.
Leptomeningeal carcinomatosis (LC) is a severe complication in the advanced stage of lung adenocarcinoma, with an extremely poor prognosis. Currently, the diagnosis of LC poses challenges. Serum exosomal miRNAs (microRNAs) have been demonstrated to possess potential as viable biomarkers. However, their value in the diagnosis of LC remains unclear.
In this study, serum samples were collected from lung adenocarcinoma patients with LC. The control groups consisted of patients with early-stage and advanced-stage lung adenocarcinoma without LC. Serum exosomes were isolated for high - throughput RNA sequencing to screen for differential miRNAs, and the results were validated in 123 samples. Subsequently, the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of exosomal miRNAs for LC.
The results of miRNA sequencing revealed seven differentially enriched miRNAs (miRNA-1296-5p, miR-503-5p, miR-499a-5p, miR-374a-5p, miR-3173-5p, miR-370-3p and miR-885-3p). The ddPCR confirmed that the expression levels of miRNA-1296-5p, miR-499a-5p and miR-374a-5p were significantly elevated in LC, while miR-370-3p was significantly decreased (P < 0.05). ROC curve analysis showed that the AUC of the combination of miRNA-1296-5p, miR-499a-5p and miR-370-3p with CEA was 0.803 (P < 0.0001), displaying higher diagnostic power for LC.
This study suggests that the specific expression of miRNA-1296-5p, miR-499a-5p, miR-374a-5p and miR-370-3p in the serum exosomes of LC, which has diagnostic potential. And the combination of miRNA-1296-5p, miR-499a-5p and miR-370-3p with CEA can further enhance this potential.
软脑膜癌病(LC)是肺腺癌晚期的一种严重并发症,预后极差。目前,LC的诊断存在挑战。血清外泌体微小RNA(miRNA)已被证明有作为可行生物标志物的潜力。然而,它们在LC诊断中的价值仍不明确。
在本研究中,收集了患有LC的肺腺癌患者的血清样本。对照组由无LC的早期和晚期肺腺癌患者组成。分离血清外泌体用于高通量RNA测序以筛选差异miRNA,并在123个样本中验证结果。随后,使用受试者工作特征(ROC)曲线评估外泌体miRNA对LC的诊断能力。
miRNA测序结果显示7种差异富集的miRNA(miRNA-1296-5p、miR-503-5p、miR-499a-5p、miR-374a-5p、miR-3173-5p、miR-370-3p和miR-885-3p)。数字PCR证实miRNA-1296-5p、miR-499a-5p和miR-374a-5p在LC中的表达水平显著升高,而miR-370-3p显著降低(P<0.05)。ROC曲线分析表明,miRNA-1296-5p、miR-499a-5p和miR-370-3p与癌胚抗原(CEA)联合检测的曲线下面积(AUC)为0.803(P<0.0001),对LC显示出更高的诊断效能。
本研究表明,miRNA-1296-5p、miR-499a-5p、miR-374a-5p和miR-370-3p在LC血清外泌体中的特异性表达具有诊断潜力。并且miRNA-1296-5p、miR-499a-5p和miR-370-3p与CEA联合检测可进一步增强这种潜力。