Screening and Identification of Key Microenvironment-Related Genes in Non-functioning Pituitary Adenoma.
Screening and Identification of Key Microenvironment-Related Genes in Non-functioning Pituitary Adenoma.
复制标题
无功能垂体腺瘤微环境关键基因的筛选与鉴定
DOI：
10.3389/fgene.2021.627117
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发表时间：
2021
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Guo J;Fang Q;Liu Y;Xie W;Li C;Zhang Y
目的无功能垂体腺瘤（NFPA）是一种非常常见的颅内肿瘤，具有局部侵袭性，复发率高。肿瘤微环境（TME）与肿瘤的发生、发展及预后密切相关。本研究旨在鉴定NFPA中微环境相关基因并评估其预后价值。方法收集北京天坛医院73例NFPA肿瘤标本，采用基因芯片技术分析其转录表达谱。通过ESTIMATE算法计算每个样本的免疫和基质评分，并将患者分为高和低免疫/基质评分组。然后获得交叉差异表达基因（DEG），构建蛋白质-蛋白质相互作用（PPI）网络。然后通过基因本体论和京都基因和基因组百科全书分析交叉DEG的潜在功能和途径。评估这些基因的预后价值。在另一组NFPA样本中使用定量实时聚合酶链反应来确认生物信息学分析的可信度。结果免疫/间质评分与海绵窦（CS）浸润密切相关。Kaplan-Meier曲线显示高免疫评分组与低无复发生存率显著相关。我们根据高与低免疫/基质评分组确定了497个交叉DEG。对PPI网络中497个DEG和hub基因的功能富集分析表明，这些基因主要参与免疫/炎症反应、T细胞活化和磷脂酰肌醇3激酶-蛋白激酶B信号通路。在交叉DEG中，进一步验证了88个基因在CS侵袭性组和非侵袭性组之间显著表达，并且5个基因与NFPA预后高度相关。结论筛选出一系列与NFPA中TME相关的关键基因。这些基因可能在NFPA的发展和预后中发挥重要作用，并可能产生新的治疗靶点。
Purpose Non-functioning pituitary adenoma (NFPA) is a very common type of intracranial tumor, which can be locally invasive and can have a high recurrence rate. The tumor microenvironment (TME) shows a high correlation with tumor pathogenesis and prognosis. The current study aimed to identify microenvironment-related genes in NFPAs and assess their prognostic value. Methods 73 NFPA tumor samples were collected from Beijing Tiantan Hospital and transcriptional expression profiles were obtained through microarray analysis. The immune and stromal scores of each sample were calculated through the ESTIMATE algorithm, and the patients were divided into high and low immune/stromal score groups. Intersection differentially expressed genes (DEGs) were then obtained to construct a protein–protein interaction (PPI) network. Potential functions and pathways of intersection DEGs were then analyzed through Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The prognostic value of these genes was evaluated. The quantitative real-time polymerase chain reaction in another set of NFPA samples was used to confirm the credibility of the bioinformatics analysis. Results The immune/stromal scores were significantly correlated with cavernous sinus (CS) invasion. The Kaplan–Meier curve indicated that the high immune score group was significantly related to poor recurrence-free survival. We identified 497 intersection DEGs based on the high vs. low immune/stromal score groups. Function enrichment analyses of 497 DEGs and hub genes from the PPI network showed that these genes are mainly involved in the immune/inflammatory response, T cell activation, and the phosphatidylinositol 3 kinase-protein kinase B signaling pathway. Among the intersection DEGs, 88 genes were further verified as significantly expressed between the CS invasive group and the non-invasive group, and five genes were highly associated with NFPA prognosis. Conclusion We screened out a series of critical genes associated with the TME in NFPAs. These genes may play a fundamental role in the development and prognosis of NFPA and may yield new therapeutic targets.