KIF11 Serves as an Independent Prognostic Factor and Therapeutic Target for Patients With Lung Adenocarcinoma.
KIF11 Serves as an Independent Prognostic Factor and Therapeutic Target for Patients With Lung Adenocarcinoma.
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DOI：
10.3389/fonc.2021.670218
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发表时间：
2021
影响因子：
4.7
通讯作者：
Li F
中科院分区：
文献类型：
--
作者：
Li Z;Yu B;Qi F;Li F
由于对分子机制了解甚少且治疗靶点有限，肺腺癌（LUAD）在临床实践中面临挑战。在此，这项工作旨在利用生物信息学来确定 LUAD 治疗有希望的分子靶点。使用癌症基因组图谱（TCGA）数据集中的差异表达基因（DEG）进行加权基因共表达网络分析（WGCNA）以筛选中心基因。通过荟萃分析和COX回归分析进行预后评估后，我们对相应基因进行了功能分析。采用ESTIMATE和CIBERSORT方法分析hub基因与肿瘤微环境（TME）的关联。进行了一组功能测定，以确定 hub 基因在 A549 和 PC-9 细胞中的功能作用。我们的筛选将 KIF11 确定为预后因素，这表明 LUAD 患者的总生存期较差，无进展生存期较差。此外，KIF11 主要参与细胞周期、TME 改变和肿瘤浸润免疫细胞比例。 KIF11 敲低对细胞增殖、迁移和侵袭产生抑制作用。流式细胞术分析结果显示，KIF11 敲低可诱导 LUAD 细胞 G2/M 期停滞并改善细胞凋亡。 KIF11对于LUAD细胞增殖和转移至关重要，它可能作为LUAD患者的独立预后因素以及有希望的治疗靶点。
Lung adenocarcinoma (LUAD) is challenging in clinical practice due to the poor understanding of molecular mechanisms and limited therapeutic targets. Herein, the work aimed to use bioinformatics to identify a promising molecular target for LUAD therapy. Differentially expressed genes (DEGs) from the Cancer Genome Atlas (TCGA) dataset were used for a weighted gene co-expression network analysis (WGCNA) to screen the hub gene. After a prognostic estimation with meta-analysis and COX regression analysis, we performed a function analysis on the corresponding gene. The ESTIMATE and CIBERSORT methods were adopted to analyze the association of the hub gene with the tumor microenvironment (TME). A cohort of functional assays was conducted to establish the functional roles of the hub gene in A549 and PC-9 cells. Our screen identified KIF11 as a prognostic factor, which indicated the poor overall survival and the worse progression-free survival in LUAD patients. Additionally, KIF11 was primarily involved in cell cycle, TME alteration and tumor-infiltrating immune cells proportions. KIF11 knockdown exerted inhibitory effects on cell proliferation, migration, and invasion. Results of the flow cytometry analysis revealed that KIF11 knockdown induced a G2/M phase arrest and improved apoptosis in LUAD cells. KIF11 is essential for LUAD cell proliferation and metastasis, and it may serve as an independent prognostic factor as well as a promising therapeutic target for LUAD patients.
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