PDF(Pubmed)
Abstract：
Family with sequence similarity 72B (FAM72B) has been characterized in the regulation of neuronal development. Nevertheless, the prognostic value of FAM72B expression and its function in the immune microenvironment of lung adenocarcinoma (LUAD) currently remains elusive. In this study, by adopting bioinformatics methodology and experimental verification, we found that FAM72B was upregulated in lung cancer tissues and cell lines, and a higher FAM72B level predicted an unfavorable clinical outcome in LUAD patients. The knockdown of FAM72B significantly inhibited cell proliferation, cell migration, and induced cell apoptosis in LUAD. The receiver operating characteristic curve suggested that FAM72B had a high predictive accuracy for the outcomes of LUAD. Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analyses confirmed that FAM72B-related genes were involved in cell proliferation and immune-response signaling pathway. Moreover, upregulated FAM72B expression was significantly associated with immune cell infiltration in the LUAD tumor microenvironment. Meanwhile, a potential ceRNA network was constructed to identify the lncRNA-AL360270.2/TMPO-AS1/AC125807.2/has-let-7a/7b/7c/7e/7f/FAM72B regulatory axis that regulates FAM72B overexpression in LUAD and is associated with a poor prognosis. We also confirmed that AL360270.2, TMPO-AS1, and AC125807.2 were significantly upregulated in LUAD cell lines than in human bronchial epithelial cells. In conclusion, FAM72B may serve as a novel biomarker in predicting the clinical prognosis and immune status for lung adenocarcinoma.
摘要：
具有序列相似性的家族72B(FAM72B)已经在神经元发育的调节中被表征。然而，FAM72B的表达及其在肺腺癌（LUAD）免疫微环境中的功能的预后价值目前尚不清楚。在这项研究中,通过采用生物信息学方法和实验验证，我们发现FAM72B在肺癌组织和细胞系中上调，较高的FAM72B水平预示了LUAD患者的不良临床结局。FAM72B的敲除显著抑制细胞增殖,细胞迁移，并诱导LUAD细胞凋亡。受试者工作特征曲线表明FAM72B对LUAD的结果具有很高的预测准确性。京都基因和基因组百科全书和基因集富集分析证实，FAM72B相关基因参与细胞增殖和免疫应答信号通路。此外，在LUAD肿瘤微环境中，FAM72B表达上调与免疫细胞浸润显著相关。同时,我们构建了一个潜在的ceRNA网络,以鉴定lncRNA-AL360270.2/TMPO-AS1/AC125807.2/has-let-7a/7b/7c/7e/7f/FAM72B调节轴,该调节轴在LUAD中调节FAM72B过表达,并与不良预后相关.我们还证实，AL360270.2，TMPO-AS1和AC125807.2在LUAD细胞系中的表达明显高于人支气管上皮细胞。总之,FAM72B可作为预测肺腺癌临床预后和免疫状态的新生物标志物。
