Zhang Lingling, Liang Jianfeng, Han Zhiyi, Wang Lihua, Liang Jun, Zhang Shucai
Department of Oncology, Peking University International Hospital, Beijing, China.
Department of Neurosurgery, Peking University International Hospital, Beijing, China.
Ann Transl Med. 2022 Dec;10(24):1389. doi: 10.21037/atm-22-5703.
Brain metastasis (BM) is the main cause of death of individuals with lung adenocarcinoma (LAC). Biomarkers with high sensitivity and specificity for the early detection and treatment of BM of LAC urgently need to be identified. In this study, we analyzed the pathogenesis of LAC-induced BM by detecting micro-ribonucleic acid (miRNA) and proteome expression differences between primary LAC lesion and BM tissue specimens to identify biomarkers of LAC-associated BM and develop potential therapeutic targets.
The miRNA and protein profiles of non-metastatic primary LAC and BM cases were examined to further explore the mechanism of BM. The roles and interactions of differential miRNAs and proteins were subject to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The interactions of differential miRNAs and proteins were analyzed by R software and depicted using Cytoscape.
Compared to the LAC tissue specimens, 16 and 4 miRNAs showed increased and reduced levels, respectively, in the BM tissue specimens, and 53 proteins were upregulated, and 35 proteins were downregulated. The enrichment pathway analysis showed the nuclear factor kappa B (NF-κB) signaling and the primary immunodeficiency pathways played important roles in the pathogenetic mechanisms of BM in LAC.
This study extended understandings of the regulatory network of miRNAs and proteins and provided novel insights into the pathogenic mechanisms of BM in LAC at the miRNA and protein levels.
脑转移（BM）是肺腺癌（LAC）患者死亡的主要原因。迫切需要鉴定出对LAC脑转移的早期检测和治疗具有高灵敏度和特异性的生物标志物。在本研究中，我们通过检测原发性LAC病灶与BM组织标本之间的微小核糖核酸（miRNA）和蛋白质组表达差异，分析LAC诱导BM的发病机制，以鉴定LAC相关BM的生物标志物并开发潜在的治疗靶点。
检测非转移性原发性LAC和BM病例的miRNA和蛋白质谱，以进一步探索BM的机制。对差异miRNA和蛋白质的作用及相互作用进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。通过R软件分析差异miRNA和蛋白质的相互作用，并使用Cytoscape进行描绘。
与LAC组织标本相比，BM组织标本中分别有16种和4种miRNA水平升高和降低，53种蛋白质上调，35种蛋白质下调。富集通路分析表明，核因子κB（NF-κB）信号通路和原发性免疫缺陷通路在LAC脑转移的发病机制中起重要作用。
本研究扩展了对miRNA和蛋白质调控网络的认识，并在miRNA和蛋白质水平上为LAC脑转移的发病机制提供了新的见解。
