Research Paper Volume 14, Issue 13 pp 5571—5589
A novel prognostic signature of metastasis-associated genes and personalized therapeutic strategy for lung adenocarcinoma patients
- 1 Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 2 Hubei University of Science and Technology, Xianning Medical College, Xianning 437100, China
Received: November 30, 2021 Accepted: June 18, 2022 Published: July 12, 2022
https://doi.org/10.18632/aging.204169How to Cite
Copyright: © 2022 Wang 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
Lung adenocarcinoma (LUAD) is a highly invasive and metastatic malignant tumor with high morbidity and mortality. This study aimed to construct a prognostic signature for LUAD patients based on metastasis-associated genes (MAGs). RNA expression profiles were downloaded from the Cancer Genome Atlas (TCGA) database. RRA method was applied to identify differentially expressed MAGs. A total of 192 significantly robust MAGs were determined among seven GEO datasets. MAGs were initially selected through the Lasso Cox regression analysis and 6 MAGs were included to construct a prognostic signature model. Transcriptome profile, patient prognosis, correlation between the risk score and clinicopathological features, immune cell infiltration characteristics, immunotherapy sensitivity and chemotherapy sensitivity differed between low- and high-risk groups after grouping according to median risk score. The reliability and applicability of the signature were further validated in the GSE31210, GSE50081 and GSE68465 cohort. CMap predicted 62 small molecule drugs on the base of the prognostic MAGs. Targeted drug staurosporine had hydrogen bonding with Gln-172 of SLC2A1, which is one of MAGs. Staurosporine could inhibit cell migration in A549 and H1299. We further verified mRNA and protein expression of 6 MAGs in A549 and H1299. The signature can serve as a promising prognostic tool and may provide a novel personalized therapeutic strategy for LUAD patients.
Abbreviations
TCGA: The Cancer Genome Atlas; LUAD: lung adenocarcinoma; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; MAGs: metastasis-associated genes; ROC: receptor operating characteristic; OS: Overall Survival; PFS: progression-free survival.