{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:27:31Z","timestamp":1783078051306,"version":"3.54.6"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      C-ion irradiation exerts a dual anti-proliferative effect on lung adenocarcinoma cells: it directly induces DNA damage (increased \u03b3-H2AX\/53BP1 foci), suppresses clonogenic survival, and inhibits tumor cell migration and invasion (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 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 (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05). Carbon ion radiation suppressed GCH1 expression and promoted the expression of CPT1 and EPAS1 in tumor tissues (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1802182","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:10:12Z","timestamp":1783077012000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics integration reveals inhibitory effects of carbon ion radiation on lung adenocarcinoma proliferation"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhen","family":"Yang","sequence":"first","affiliation":[{"name":"Gansu Provincial Peoples Hospital","place":["Lanzhou, China"]},{"name":"Institute of Modern Physics, Chinese Academy of Sciences","place":["Lanzhou, China"]},{"name":"School of Public Health, Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangwu","family":"Feng","sequence":"additional","affiliation":[{"name":"Gansu Provincial Peoples Hospital","place":["Lanzhou, China"]},{"name":"Institute of Modern Physics, Chinese Academy of Sciences","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiucai","family":"Ma","sequence":"additional","affiliation":[{"name":"Gansu Provincial Peoples Hospital","place":["Lanzhou, 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