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.

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.

• Authors: Qiang Guo, Kai Li, Ni Jiang, Rui Zhou, Xin-Rui Rao, Chuang-Yan Wu
• Journal: Aging (Aging (Albany NY)) Vol. 15 Issue 18 Pg. 9633-9660 (09 21 2023) ISSN: 1945-4589 [Electronic] United States
• PMID: 37737707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gefitinib
• Aurora Kinase A
• AURKA protein, human

Topics

• Humans
• Gefitinib (pharmacology, therapeutic use)
• Aurora Kinase A (genetics)
• Prognosis
• Adenocarcinoma of Lung (drug therapy, genetics)
• Lung Neoplasms (drug therapy, genetics)
• Tumor Microenvironment (genetics)