KIF11 Serves as an Independent Prognostic Factor and Therapeutic Target for Patients With Lung Adenocarcinoma
Zhaodong Li1, Bingxin Yu2, Fangyuan Qi1
1Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
KIF11 is a key factor in lung adenocarcinoma (LUAD) progression, impacting survival and metastasis. Targeting KIF11 shows promise for new LUAD therapies.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Lung adenocarcinoma (LUAD) presents clinical challenges due to poorly understood molecular mechanisms and limited therapeutic options.
- Identifying novel molecular targets is crucial for improving LUAD treatment outcomes.
Purpose of the Study:
- To identify a promising molecular target for lung adenocarcinoma (LUAD) therapy using bioinformatics approaches.
- To investigate the role of the identified hub gene in LUAD progression and its association with the tumor microenvironment.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) on TCGA data to identify hub genes.
- Prognostic estimation using meta-analysis and COX regression.
- Functional assays (e.g., cell proliferation, migration, invasion, flow cytometry) in LUAD cell lines.
Main Results:
- KIF11 was identified as a significant prognostic factor, correlating with poor overall and progression-free survival in LUAD patients.
- KIF11 knockdown inhibited LUAD cell proliferation, migration, and invasion, inducing G2/M phase arrest and apoptosis.
- KIF11 expression is linked to cell cycle regulation, tumor microenvironment alterations, and immune cell infiltration.
Conclusions:
- KIF11 plays an essential role in LUAD cell proliferation and metastasis.
- KIF11 may serve as an independent prognostic biomarker and a promising therapeutic target for LUAD.
More Related Videos
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
