Research Paper Volume 15, Issue 18 pp 9633—9660
A novel risk model of three gefitinib-related genes FBP1, SBK1 and AURKA is related to the immune microenvironment and is predicting prognosis of lung adenocarcinoma patients
- 1 Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2 Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- 3 Department of Hepatobiliary and Pancreatic Surgery, The People’s Hospital of Jianyang City, Jianyang, China
- 4 Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
- 5 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 6 Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Received: May 24, 2023 Accepted: August 21, 2023 Published: September 21, 2023
https://doi.org/10.18632/aging.205040How to Cite
Copyright: © 2023 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Purpose: Gefitinib, an anticancer drug, has been reported to potentially improve the prognosis of patients with lung adenocarcinoma (LUAD). This study aims to investigate the roles and mechanisms of Gefitinib.
Methods: The effects of Gefitinib on the growth and migration of LUAD cells were assessed using various methods, including CCK-8, flow cytometry, wound healing, and Transwell assays. To analyze the function and mechanisms of the differentially expressed Gefitinib target genes (GTGs), data from the TCGA database were utilized. Kaplan-Meier survival and ROC analysis identified prognostic-related GTGs and constructed a prognostic nomogram in LUAD. Consensus clustering, COX analysis and survival analysis evaluated the relationship between GTGs and the prognosis of LUAD patients. The mechanisms of the risk model involved LUAD progression, and the relationship between the risk model and immune microenvironment were investigated.
Results: Gefitinib could inhibit proliferation, migration and invasion and promote cell apoptosis. 84 DEGTGs were involved in RAS, MAPK, ERBB pathways. The DEGTGs (FBP1, SBK1, and AURKA) were the independent risk factors for dismal prognosis of LUAD patients and were used to establish risk model and nomogram. Gefitinib could promote the expression of FBP1 and inhibit the expression of SBK1 and AURKA. High-risk LUAD patients had the dismal prognosis, and the high-risk score group was significantly associated with the immune microenvironment.
Conclusion: FBP1, SBK1, and AURKA are prognostic risk factors, and the risk model and nomogram of FBP1, SBK1 and AURKA are associated with dismal prognosis and immune cell infiltration, and have huge prospects for application in evaluating the prognosis in LUAD.
Abbreviations
LUAD: lung adenocarcinoma; PFS: progression-free survival; OS: overall survival; TCGA: the cancer genome atlas; DEGTGs: differentially expressed Gefitinib target genes; GO: gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: protein-protein interaction; PCA: Principal component analysis; DEG: differentially expressed genes.