Gene Signatures for Latent Radiation-Induced Lung Injury Post X-ray Exposure in Mouse

Tongtong Zhang; Zhaoming Zhou; Lei Wen; Changguo Shan; Mingyao Lai; Jing Liao; Xin Zeng; Gang Yan; Linbo Cai; Meijuan Zhou; Minghua Wang

doi:10.1177/15593258231178146

Gene Signatures for Latent Radiation-Induced Lung Injury Post X-ray Exposure in Mouse

Dose Response. 2023 Jun 28;21(2):15593258231178146. doi: 10.1177/15593258231178146. eCollection 2023 Apr-Jun.

Authors

Tongtong Zhang¹, Zhaoming Zhou^{2

3}, Lei Wen⁴, Changguo Shan⁴, Mingyao Lai⁴, Jing Liao², Xin Zeng², Gang Yan¹, Linbo Cai⁴, Meijuan Zhou², Minghua Wang¹

Affiliations

¹ Department of Nuclear Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
² Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
³ Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China.
⁴ Oncology Department, Guangdong Sanjiu Brain Hospital, Guangzhou, China.

Abstract

Objective: To investigate the X-ray-specific sensitive genes and potential signaling pathways involved in the latent period of radiation-induced lung injury (RILI) in mouse models.

Method: Mice were randomized into groups for whole thoracic irradiation with a single fraction of 20 Gy X-ray or 12.5 Gy carbon heavy ion. Lungs were harvested 3 weeks after the irradiation, whole RNA was extracted and detected with the genome-wide transcriptional microarrays. Differentially expressed genes (DEGs) were calculated for each group and the X-ray-specific sensitive genes were determined, followed by the gene enrichment analysis of those DEGs exploring the potentially relevant signaling pathways and biological processes in latent RILI.

Results: Three weeks after irradiation, gene expression levels varied between groups. 76 up-regulated DEGs were determined with mice in the X-ray group and gene ontology enrichment analysis for biological process (GO-BP) obtained several processes which were associated with radiation reaction, mitotic, immune cell chemotaxis or metastasis, immune factors, p53 apoptosis, and tissue remodeling. KEGG signaling pathway enrichment analysis showed that those 76 up-regulated DEGs were enriched in p53, IL-17, FoXO, melanoma, and non-small-cell lung cancer signaling pathways. By comparing the DEGs in X-ray and heavy ion groups, X-ray-specific sensitive genes were determined, the top 10 genes were Adamts9, Aacs, Col6a2, Fdps, Mdk, Mcam, Stbd1, Lbh, Ak3, and Emid1. The expression level of the top 10 genes was found to be significantly higher in the X-ray group than in the control and heavy ion groups.

Conclusion: Our research determined the X-ray-specific sensitive gene set in mice lungs after exposure to radiation. The gene set could be used as a genetic marker to suggest the latency of RILI. The enrichment analysis results suggested that the relevant signaling pathways were potentially involved in the development of RILI. Further validation of those genes and signaling pathways is needed to confirm these findings.

Keywords: X-ray-specific; gene signatures; genome-wide transcriptional profiling; radiation-induced lung injury; signaling pathway.