Back to Search Start Over

SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion

SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion

Authors :
Yafeng Liu
Tao Han
Jing Wu
Jiawei Zhou
Jianqiang Guo
Rui Miao
Zhi Xu
Yingru Xing
Ying Bai
Dong Hu
Source :
Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-21 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

Abstract Background The occurrence of epithelial-mesenchymal transition (EMT) and immune evasion is considered to contribute to poor prognosis in lung adenocarcinoma (LUAD). Therefore, this study aims to explore the key oncogenes that promote EMT and immune evasion and reveal the expression patterns, prognostic value, and potential biological functions. Methods Firstly, we identified gene modules associated with EMT and Tumor Immune Dysfunction and Exclusion (TIDE) through weighted gene co-expression network analysis (WGCNA). Next, we utilized differential analysis and machine learning to identify the key genes and validate them. Moreover, we analyzed the correlation between key genes and tumor microenvironment remodeling, drug sensitivity, as well as mutation frequency. Furthermore, we explored and validated their malignant biological characteristics through in vitro experiments and clinical samples. Finally, potential drugs for LUAD were screened based on CMap and validated through experiments. Results Firstly, WGCNA analysis revealed that red and green modules were highly correlated with EMT and TIDE. Among them, upregulated expression of SPOCK1 was observed in lung adenocarcinoma tissues and was associated with poor prognosis. Additionally, patients in the high SPOCK1 group showed more activation of malignant oncogenic pathways, higher infiltration of immunosuppressive components, and a higher frequency of mutations. The knockdown of SPOCK1 suppressed invasion and metastasis capabilities of lung adenocarcinoma cells, and the high expression of SPOCK1 was associated with low infiltration of CD8+ T cells. Therapeutic aspects, SPOCK1 can be a candidate indicator for drug sensitivity and CMap showed that VER-155008 was the drug candidate with the largest perturbation effect on the SPOCK1 expression profile. In vitro and in vivo experiments validated the cancer-inhibitory effect of VER-155008 in LUAD. Conclusion This study revealed through comprehensive bioinformatics analysis and experimental analysis that SPOCK1 can promote EMT and immune escape in LUAD, and it may serve as a promising candidate prognostic biomarker and therapeutic target for LUAD.

Details

Language :
English
ISSN :
14795876
Volume :
21
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Translational Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.0c12cef9c507428a8846cb4920f956ed
Document Type :
article
Full Text :
https://doi.org/10.1186/s12967-023-04616-3