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PI3K/Akt 信号通路相关长非编码 RNA 标志物预测喉癌患者的预后。

PI3K/Akt signalling pathway-associated long noncoding RNA signature predicts the prognosis of laryngeal cancer patients.

机构信息

Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Hebei, 050000, China.

出版信息

Sci Rep. 2023 Sep 7;13(1):14764. doi: 10.1038/s41598-023-41927-3.

Abstract

The PI3K/Akt signalling pathway is associated with the occurrence and development of tumours and significantly affects the prognosis of patients. We established a predictive signature based on the PI3K/Akt pathway to predict the prognosis of patients. The RNA-seq and clinical data of laryngeal cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. Three lncRNAs (MNX1-AS1, LINC00330, LSAMP-AS1) were selected through univariate, multivariate Cox and log-rank test analysis to establish a prognostic signature. The patients were then divided into high-risk and low-risk groups based on their risk score. In the TCGA training set, the survival time of the high-risk group was shorter than that of the low-risk group (P < 0.01). Follicular helper T cells were lower in the high-risk group (P = 0.022), and CCR, inflammation promotion, parainflammation, and type I IFN immune function were suppressed. The results of the drug sensitivity analysis suggest that the high-risk group is sensitive to AKT inhibitors. The establishment of the signature was also verified based on the clinical data. Three lncRNAs can facilitate the migration, invasion, and vitality of cancer cells in vitro, and vice versa. Moreover, p-AKT (Ser473) and p-PI3K were highly activated in the cells overexpressing the abovementioned three lncRNAs. The PI3K/Akt signalling pathway-associated prognosis signature has a good predictive effect.

摘要

PI3K/Akt 信号通路与肿瘤的发生和发展有关,显著影响患者的预后。我们建立了一个基于 PI3K/Akt 通路的预测性特征,以预测患者的预后。从癌症基因组图谱 (TCGA) 数据库下载了喉癌患者的 RNA-seq 和临床数据。通过单因素、多因素 Cox 和对数秩检验分析,选择了三个 lncRNA(MNX1-AS1、LINC00330、LSAMP-AS1)来建立预后特征。然后根据风险评分将患者分为高风险组和低风险组。在 TCGA 训练集中,高风险组的生存时间短于低风险组(P<0.01)。高风险组滤泡辅助 T 细胞较低(P=0.022),CCR、炎症促进、副炎症和 I 型 IFN 免疫功能受到抑制。药物敏感性分析的结果表明,高风险组对 AKT 抑制剂敏感。该特征的建立也基于临床数据进行了验证。三个 lncRNA 可以促进癌细胞在体外的迁移、侵袭和活力,反之亦然。此外,在过表达上述三个 lncRNA 的细胞中,p-AKT(Ser473)和 p-PI3K 被高度激活。PI3K/Akt 信号通路相关的预后特征具有良好的预测效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9555/10485045/8702afbbc194/41598_2023_41927_Fig1_HTML.jpg

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