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- Title
Identification of a novel autophagy signature for predicting survival in patients with lung adenocarcinoma.
- Authors
Jin Duan; Youming Lei; Guoli Lv; Yinqiang Liu; Wei Zhao; Qingmei Yang; Xiaona Su; Zhijian Song; Leilei Lu; Yunfei Shi
- Abstract
Background. Lung adenocarcinoma (LUAD) is the most commonhistological lung cancer subtype, with an overall five-year survivalrate of only 17%. In this study, we aimed to identify autophagy-related genes (ARGs) and develop an LUAD prognostic signature. Methods. In this study, we obtained ARGs from three databases and downloaded gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We used TCGA-LUAD (nD490) for a training and testing dataset, and GSE50081 (nD127) as the external validation dataset. The least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature. We performed gene set enrichment analysis (GSEA) and immune cell analysis between the high- and low-risk groups. A nomogram was built to guide the individual treatment for LUAD patients. Results. We identified a total of 83 differentially expressed ARGs (DEARGs) from the TCGA-LUAD dataset, including 33 upregulated DEARGs and 50 downregulated DEARGs, both with thresholds of adjusted P < 0:05 and jFold changej > 1:5. Using LASSO and multivariate Cox regression analyses, we identified 10 ARGs that we used to build a prognostic signature with areas under the curve (AUCs) of 0.705, 0.715, and 0.778 at 1, 3, and 5 years, respectively. Using the risk score formula, the LUAD patients were divided into low- or high-risk groups. Our GSEA results suggested that the low-risk group were enriched in metabolism and immune-related pathways, while the high-risk group was involved in tumorigenesis and tumor progression pathways. Immune cell analysis revealed that, when compared to the high-risk group, the low- risk group had a lower cell fraction of M0- and M1- macrophages, and higher CD4 and PD-L1 expression levels. Conclusion. Our identified robust signature may provide novel insight into underlying autophagy mechanisms as well as therapeutic strategies for LUAD treatment.
- Subjects
GENE expression profiling; AUTOPHAGY; CELL analysis; ADENOCARCINOMA; LUNGS
- Publication
PeerJ, 2021, p1
- ISSN
2167-8359
- Publication type
Article
- DOI
10.7717/peerj.11074