Background/Objectives: Brain metastases (BM) are the most common type of intracranial malignant tumor and are associated with high mortality. More than 50% of BM cases originate from lung cancer, and lung adenocarcinoma (LUAD) is most commonly associated with the development of BM (25%). The differential diagnosis of solitary BM and glioblastoma (GBM)—one of the most aggressive and fatal malignant brain tumors—remains a considerable challenge. Given the major role of microRNAs (miRNAs) in regulating gene expression, their clinical potential as biomarkers for tumor diagnosis and prognosis offers significant promise. Methods: Next-generation RNA Sequencing (RNA-seq) was used to assess the miRNA expression profiles of 6 LUAD-BM, 6 GBM, and 6 control (non-tumoral brain tissue samples) human brain tissue samples. miRNAs exhibiting the most significant differential expression in LUAD-BM patients in comparison to both control subjects and GBM patients were selected for validation through RT-qPCR. Results: The analysis of RNA-seq data revealed the presence of 229 differentially expressed miRNAs in the comparison between LUAD-BM and control samples and 46 in the comparison between LU-AD-BM and GBM samples. Eight miRNAs were selected for further analysis, four of which were upregulated and four downregulated, based on the significant differences in their expression levels observed between the LUAD-BM samples and the other two groups, as confirmed with the Mann–Whitney U test. Functional enrichment analysis was also conducted based on a miRNA-centered target analysis performed using the miRNet tool. To assess the diagnostic potential of these differentially expressed miRNAs, we performed a receiver operating characteristic (ROC) curve analysis. Conclusions: A panel of eight miRNAs was identified in human brain tissue samples, exhibiting high accuracy in distinguishing LUAD-BM from both GBM and control samples.
背景/目的：脑转移瘤是最常见的颅内恶性肿瘤类型，与高死亡率相关。超过50%的脑转移瘤病例源自肺癌，其中肺腺癌最常与脑转移瘤的发生相关（25%）。孤立性脑转移瘤与最具侵袭性和致命性的恶性脑肿瘤之一——胶质母细胞瘤的鉴别诊断仍然是一个重大挑战。鉴于微小RNA在调控基因表达中的重要作用，其作为肿瘤诊断和预后生物标志物的临床潜力具有重大前景。方法：采用新一代RNA测序技术评估了6例肺腺癌脑转移瘤、6例胶质母细胞瘤及6例对照（非肿瘤脑组织样本）的人脑组织样本中的miRNA表达谱。通过RT-qPCR验证了在肺腺癌脑转移瘤患者中相较于对照组和胶质母细胞瘤患者表达差异最显著的miRNA。结果：RNA-seq数据分析显示，在肺腺癌脑转移瘤与对照样本的比较中存在229个差异表达miRNA，在肺腺癌脑转移瘤与胶质母细胞瘤样本的比较中存在46个差异表达miRNA。根据肺腺癌脑转移瘤样本与其他两组间观察到的显著表达差异（经Mann-Whitney U检验证实），筛选出8个miRNA进行深入分析，其中4个上调、4个下调。基于使用miRNet工具进行的以miRNA为中心的靶标分析，还进行了功能富集分析。为评估这些差异表达miRNA的诊断潜力，我们进行了受试者工作特征曲线分析。结论：在人脑组织样本中鉴定出一组包含8个miRNA的标志物，其在区分肺腺癌脑转移瘤与胶质母细胞瘤及对照样本方面表现出高准确性。
肿瘤(癌症)患者之家