Comprehensive multi-omics analysis identifies BTG2 as a potential regulator of radiotherapy response in lung adenocarcinoma.
8 affiliations
- 1Department of Thoracic Surgery, The Cancer Hospital of the Chinese Academy of Medical Sciences, Shenzhen Center, Southern University of Science and Technology, Shenzhen, Guangdong, China; Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- 2Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
- 3Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- 4Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN, USA.
- 5Department of Radiotherapy, The First Hospital of China Medical University, Shenyang, Liaoning, China.
- 6Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei, China. Electronic address: [email protected].
- 7Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Radiotherapy, The First Hospital of China Medical University, Shenyang, Liaoning, China. Electronic address: [email protected].
- 8Department of Radiation Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei, China. Electronic address: [email protected].
Abstract
Lung adenocarcinoma (LUAD) is one of the most common malignancies worldwide. However, patients exhibit heterogeneous responses to radiotherapy, and a subset of individuals develops resistance, which severely compromises clinical outcomes. The underlying molecular basis of this variability remains unclear. This study aimed to investigate RSG-associated molecular features in radiotherapy-treated LUAD and to identify potential prognostic biomarkers. We integrated multi-omics data and applied multiple machine learning approaches to comprehensively analyze LUAD samples. In addition, single-cell data were incorporated to further characterize the tumor microenvironment. The results revealed two distinct RSG-associated prognostic subtypes with different survival outcomes and biological characteristics. The poor-prognosis subtype was associated with significant alterations in the immune microenvironment and related biological pathways. Furthermore, we developed a predictive model with stable performance for evaluating patient survival outcomes. Among the identified candidates, BTG2 emerged as a key gene in the RSG-based prognostic model. Functional experiments further showed that BTG2 overexpression inhibited tumor cell proliferation. Bidirectional clonogenic radiation dose-response assays showed lower post-irradiation survival after BTG2 overexpression and higher survival after BTG2 depletion, supporting BTG2 as a cellular modulator of radiation response. In summary, this study identified two RSG-associated prognostic subtypes among radiotherapy-treated patients with LUAD and highlighted BTG2 as a potential biomarker associated with prognosis and radiation-response-related biological features. These findings provide a framework for further prospective validation and may contribute to future risk stratification and individualized treatment strategies.
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BibTeX
@article{wang2026comprehensive,
title = {{Comprehensive multi-omics analysis identifies BTG2 as a potential regulator of radiotherapy response in lung adenocarcinoma.}},
author = {Ming-Hao Wang and Xiao-Jing Wei and Yu Wang and Dilinaer Wusiman and Yi-Tong Li and Xiao-Kai You and Hai-Ling Qie and Cheng-Yi Zhang and Xue-Feng Wang},
journal = {Neoplasia (New York, N.Y.)},
year = {2026},
month = oct,
doi = {10.1016/j.neo.2026.101377},
url = {https://europepmc.org/article/MED/42874239},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Comprehensive multi-omics analysis identifies BTG2 as a potential regulator of radiotherapy response in lung adenocarcinoma.
AU - Ming-Hao Wang
AU - Xiao-Jing Wei
AU - Yu Wang
AU - Dilinaer Wusiman
AU - Yi-Tong Li
AU - Xiao-Kai You
AU - Hai-Ling Qie
AU - Cheng-Yi Zhang
AU - Xue-Feng Wang
PY - 2026
DA - 2026/10/13
JO - Neoplasia (New York, N.Y.)
DO - 10.1016/j.neo.2026.101377
UR - https://europepmc.org/article/MED/42874239
AB - Lung adenocarcinoma (LUAD) is one of the most common malignancies worldwide. However, patients exhibit heterogeneous responses to radiotherapy, and a subset of individuals develops resistance, which severely compromises clinical outcomes. The underlying molecular basis of this variability remains unclear. This study aimed to investigate RSG-associated molecular features in radiotherapy-treated LUAD and to identify potential prognostic biomarkers. We integrated multi-omics data and applied multiple machine learning approaches to comprehensively analyze LUAD samples. In addition, single-cell data were incorporated to further characterize the tumor microenvironment. The results revealed two distinct RSG-associated prognostic subtypes with different survival outcomes and biological characteristics. The poor-prognosis subtype was associated with significant alterations in the immune microenvironment and related biological pathways. Furthermore, we developed a predictive model with stable performance for evaluating patient survival outcomes. Among the identified candidates, BTG2 emerged as a key gene in the RSG-based prognostic model. Functional experiments further showed that BTG2 overexpression inhibited tumor cell proliferation. Bidirectional clonogenic radiation dose-response assays showed lower post-irradiation survival after BTG2 overexpression and higher survival after BTG2 depletion, supporting BTG2 as a cellular modulator of radiation response. In summary, this study identified two RSG-associated prognostic subtypes among radiotherapy-treated patients with LUAD and highlighted BTG2 as a potential biomarker associated with prognosis and radiation-response-related biological features. These findings provide a framework for further prospective validation and may contribute to future risk stratification and individualized treatment strategies.
SN - 1522-8002
SN - 1476-5586
ER -