文献类型：期刊文献

英文题名：Multi-omics integration reveals inhibitory effects of carbon ion radiation on lung adenocarcinoma proliferation

作者：Yang, Zhen[1,2,3];Feng, Shuangwu[1,2];Ma, Xiucai[1];Wang, Lina[4];Sun, Shilong[2];Liu, Zhiqiang[2];Tian, Xuejiao[3];Geng, Yichao[5];Zhang, Qiuning[2,6]

第一作者：杨梓;Yang, Zhen

通信作者：Zhang, QN[1];Geng, YC[2];Zhang, QN[3]

机构：[1]Gansu Prov Peoples Hosp, Lanzhou, Peoples R China;[2]Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China;[3]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou, Peoples R China;[4]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China;[5]Affiliated Hosp Guizhou Med Univ, Dept Oncol, Guiyang, Peoples R China;[6]Lanzhou Ion Therapy Co Ltd, Lanzhou, Peoples R China

第一机构：Gansu Prov Peoples Hosp, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China;[2]corresponding author), Affiliated Hosp Guizhou Med Univ, Dept Oncol, Guiyang, Peoples R China;[3]corresponding author), Lanzhou Ion Therapy Co Ltd, Lanzhou, Peoples R China.

年份：2026

卷号：14

起止页码：1802182

外文期刊名：FRONTIERS IN PUBLIC HEALTH

收录：;Scopus(收录号：2-s2.0-105046115707);WOS:【SSCI(收录号:WOS:001828599100001)，SCI-EXPANDED(收录号:WOS:001828599100001)】；

基金：The author(s) declared that financial support was received for this work and/or its publication. The study was supported by the Central guidance local science and technology development program (24ZYQA029). The Joint Major Projects of the Science and Technology Plan of Gansu Province, China (25JRRA1196) and the Program of Introducing Talents of Discipline to Universities (No. 2023YJRC-13). This work was also supported by Guizhou Provincial Basic Research Program (Qiankehe Foundation [2024] Youth 261). Collaborative Innovation Center for Prevention and Control of Nutrition and Environment-Related Diseases with Traditional Chinese Medicine in Northwest China (ZYXT-25-9).

语种：英文

外文关键词：carbon ions; GCH1; lung adenocarcinoma; multi-omics; proliferation inhibition

摘要：Objective: To analyze the inhibitory effect of carbon ion (C-ion) radiation-induced biological effects on the proliferation of lung adenocarcinoma (LUAD) by multi-omics integration. Methods: We investigated C-ion radiation effects on LUAD cellular responses using A549 and LLC cell lines. Clonogenic survival assays, DNA damage, and metastasis quantified radiation sensitivity, while a multi-cell co-culture system (A549/Beas-2B/LLC/MLE-12) differentiated direct vs. bystander effects. Integrated transcriptomics and targeted metabolomics identified radiation-responsive genes/metabolites, with pathway analysis conducted through MetaboAnalyst 6.0. Clinical relevance of CPT1, GCH1, and EPAS1 was assessed using UCSC Xena and Kaplan-Meier Plotter survival data. Radiation-induced molecular changes were validated by RT-qPCR and immunoblotting across cell types. An A549 tumor-bearing mouse model was established, and the growth and tumor size of the tumor-bearing mice were observed after irradiation with C-ions. Blood was taken from mice after anesthesia and necropsy to detect changes in the major differential metabolism factor arachidonic acid (AA), and tumor tissues were examined to detect changes in the expression of CPT1, GCH1, and EPAS1 in the tissues. Results: C-ion irradiation exerts a dual anti-proliferative effect on lung adenocarcinoma cells: it directly induces DNA damage (increased gamma-H2AX/53BP1 foci), suppresses clonogenic survival, and inhibits tumor cell migration and invasion (p < 0.05); meanwhile, it amplifies the bystander effect from co-cultured normal cells through metabolic reprogramming, thereby enhancing overall cytotoxicity. Transcriptomic-metabolomic integration identified CPT1, GCH1, and EPAS1 as central regulators of radiation-induced metabolic suppression, with AA, 3-hydroxytetradecanoic acid, and 2-methylglutaric acid constituting critical downstream mediators. Database analysis revealed that the differential expression of CPT1, GCH1, and EPAS1 was correlated with the prognostic survival status of patients with lung adenocarcinoma. Carbon ion irradiation downregulated the expression of GCH1 and upregulated CPT1 and EPAS1. Animal experiments demonstrated that carbon ions markedly inhibited tumor proliferation in tumor-bearing mice. The level of arachidonic acid in mouse blood was significantly increased (p < 0.05). Carbon ion radiation suppressed GCH1 expression and promoted the expression of CPT1 and EPAS1 in tumor tissues (p < 0.05). Conclusion: C-ion irradiation suppresses lung adenocarcinoma through a dual mechanism involving direct induction of cellular DNA damage and a metabolically enhanced bystander effect, driven by the CPT1/GCH1/EPAS1 regulatory axis, with arachidonic acid serving as a key downstream mediator.