{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:07:36Z","timestamp":1784092056736,"version":"3.55.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52373160"],"award-info":[{"award-number":["52373160"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016073","name":"Key Technologies Research and Development Program of Anhui Province","doi-asserted-by":"publisher","award":["201904a07020092, 202304295107020050"],"award-info":[{"award-number":["201904a07020092, 202304295107020050"]}],"id":[{"id":"10.13039\/100016073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009558","name":"University Natural Science Research Project of Anhui Province","doi-asserted-by":"publisher","award":["2208085QH238, 2208085MH252"],"award-info":[{"award-number":["2208085QH238, 2208085MH252"]}],"id":[{"id":"10.13039\/501100009558","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Drug resistance and poor clinical outcomes in lung adenocarcinoma (LUAD) necessitate robust biomarkers for personalized therapy. Glycolysis reprogramming is a hallmark of cancer, but its clinical utility remains incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated TCGA and GEO transcriptomic data with Weighted gene co\u2212expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression to construct a glycolysis\u2212related prognostic signature. A nomogram combining the risk score with clinicopathological factors was developed. Drug sensitivity was predicted using the pRRophetic algorithm. qRT\u2212PCR and xenograft models using A549 and cisplatin\u2212resistant A549\/DDP cells validated the expression of candidate genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients stratified by glycolysis-related risk scores exhibited significantly distinct survival outcomes, and the glycolysis-based signature functioned as an independent prognostic factor for overall survival in LUAD. The nomogram demonstrated robust predictive performance and effectively estimated patient sensitivity to three commonly used conventional chemotherapeutic agents.\n                      <jats:italic>In vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies using A549 cells and their cisplatin-resistant derivative A549\/DDP revealed aberrant expression of\n                      <jats:italic>VIPR1<\/jats:italic>\n                      ,\n                      <jats:italic>ADRB2<\/jats:italic>\n                      ,\n                      <jats:italic>RXFP1<\/jats:italic>\n                      ,\n                      <jats:italic>PDGFB<\/jats:italic>\n                      ,\n                      <jats:italic>WNT3A<\/jats:italic>\n                      , and\n                      <jats:italic>SPRY1<\/jats:italic>\n                      in the resistant cell line and in corresponding xenograft tumor tissues. These findings suggest that glycolytic activity is closely associated with both drug resistance and clinical prognosis in LUAD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies a glycolysis-related gene signature with demonstrable utility for prognostic stratification and therapeutic response prediction in LUAD. The proposed integrative model holds promise for enhancing precision treatment decision-making through optimized risk assessment and rational selection of chemotherapeutic regimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1871582","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:38:56Z","timestamp":1784090336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioinformatics-based identification of glycolysis-related signatures associated with drug resistance and prognosis in lung adenocarcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Qian","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First Affliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fuyang Hospital of Anhui Medical University","place":["Fuyang, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Li","sequence":"additional","affiliation":[{"name":"Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, The First Affliated Hospital of University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, The First Affliated Hospital of University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadi","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]},{"name":"Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, The First Affliated Hospital of University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]},{"name":"Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, The First Affliated Hospital of University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]},{"name":"Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, The First Affliated Hospital of University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Anhui Institute of Medicine","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]},{"name":"Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, The First Affliated Hospital of University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Anhui Institute of Medicine","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2024.102693","article-title":"Global burden of lung cancer in 2022 and projections to 2050: Incidence and mortality estimates from GLOBOCAN","volume":"93","author":"Zhou","year":"2024","journal-title":"Cancer Epidemiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/s0140-6736(16)30958-8","article-title":"Lung cancer: current therapies and new targeted treatments","volume":"389","author":"Hirsch","year":"2017","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2026.124273","article-title":"Multidrug resistant non-small cell lung cancer cells exhibiting collateral sensitivity to DNA damaging drugs","volume":"391","author":"Peixoto da Silva","year":"2026","journal-title":"Life Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-025-01083-1","article-title":"Expanding targeted therapy for lung cancer","volume":"6","author":"Ballard","year":"2025","journal-title":"Nat Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1790897","DOI":"10.1097\/COC.0000000000001275","article-title":"Targeted therapies in non-small cell lung cancer: A contemporary review","volume":"17","author":"Abdelmonem","year":"2025","journal-title":"Am J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/s41392-025-02243-6","article-title":"Advances in molecular pathology and therapy of non-small cell lung cancer","volume":"10","author":"Huang","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B7","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.jare.2025.09.014","article-title":"Integrative proteomic characterization of human lung adenocarcinoma with KRAS G12 mutations reveals molecular pathogenesis","volume":"84","author":"Shi","year":"2025","journal-title":"J Adv Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.100839","article-title":"Future perspective for the application of predictive biomarker testing in advanced stage non-small cell lung cancer","volume":"38","author":"de Jager","year":"2024","journal-title":"Lancet Reg Health Eur"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1416472","article-title":"Glycolysis in the tumor microenvironment: a driver of cancer progression and a promising therapeutic target","volume":"12","author":"Zhao","year":"2024","journal-title":"Front Cell Dev Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1037341","article-title":"Targeting glycolysis in non-small cell lung cancer: Promises and challenges","volume":"13","author":"Xu","year":"2022","journal-title":"Front Pharmacol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107906","article-title":"Glycolysis: A multifaceted metabolic pathway and signaling hub","volume":"300","author":"Kierans","year":"2024","journal-title":"J Biol Chem"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.22958","article-title":"Altered energy metabolism in cancer: a unique opportunity for therapeutic intervention","volume":"14","author":"Zhang","year":"2013","journal-title":"Cancer Biol Ther"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5c15253","article-title":"Modular design of mesoporous silica nanoparticles enables bioimaging, dual chemotherapy, and combinatorial gene silencing in triple-negative breast cancer","volume":"17","author":"Rebolledo","year":"2025","journal-title":"ACS Appl Mater Interfaces"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.932098","article-title":"Photodynamic therapy of lung cancer, where are we","volume":"13","author":"Crous","year":"2022","journal-title":"Front Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.s560983","article-title":"Tumor microenvironment-responsive nanomedicine: Monitoring and modulating the tumor microenvironment for precision cancer therapy","volume":"21","author":"He","year":"2026","journal-title":"Int J Nanomedicine"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202402393","article-title":"Sleep deprivation triggers the excessive activation of ovarian primordial follicles via beta2 adrenergic receptor signaling","volume":"11","author":"Weng","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2022.07.011","article-title":"Wnt signaling: Essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders","volume":"10","author":"Vlashi","year":"2023","journal-title":"Genes Dis"},{"key":"B18","doi-asserted-by":"publisher","first-page":"33","DOI":"10.25259\/cytojournal_190_2024","article-title":"Platelet-derived growth factor subunit B overexpression promotes lung cancer tumor growth and metastasis: The role of glucose metabolism","volume":"22","author":"Feng","year":"2025","journal-title":"Cytojournal"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205300","article-title":"Integrated multi-omics analysis for lung adenocarcinoma in Xuanwei, China","volume":"15","author":"Jiang","year":"2023","journal-title":"Aging (Albany NY)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"20426","DOI":"10.1038\/s41598-025-06294-1","article-title":"ADCY4 inhibits cAMP-induced growth of breast cancer by inactivating FAK\/AKT and ERK signaling but is frequently silenced by DNA methylation","volume":"15","author":"Pan","year":"2025","journal-title":"Sci Rep"},{"key":"B21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s13046-025-03289-8","article-title":"Suppression of SPRY1 reduces HIF1alpha-dependent glycolysis and impairs angiogenesis in BRAF-mutant cutaneous melanoma","volume":"44","author":"Montico","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12943-024-02119-3","article-title":"Altered metabolism in cancer: insights into energy pathways and therapeutic targets","volume":"23","author":"Tufail","year":"2024","journal-title":"Mol Cancer"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2025106","article-title":"Energy stress and adaptation strategy of tumor cells in different microenvironments: from primary tumors to distant metastases","volume":"58","author":"Xu","year":"2025","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2024.101076","article-title":"The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities","volume":"58","author":"Cordani","year":"2024","journal-title":"Neoplasia"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-023-01395-2","article-title":"A parallel glycolysis provides a selective advantage through rapid growth acceleration","volume":"20","author":"Law","year":"2024","journal-title":"Nat Chem Biol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2409509121","article-title":"The Warburg effect is the result of faster ATP production by glycolysis than respiration","volume":"121","author":"Kukurugya","year":"2024","journal-title":"Proc Natl Acad Sci USA"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.06.026","article-title":"100 years of the Warburg effect: A cancer metabolism endeavor","volume":"187","author":"Fendt","year":"2024","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-025-05303-1","article-title":"Glycosylation in cancer: mechanisms, diagnostic markers, and therapeutic applications","volume":"480","author":"Qusairy","year":"2025","journal-title":"Mol Cell Biochem"},{"key":"B29","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00335-026-10202-x","article-title":"Hypoxia-induced circ_0017521 enhances glycolysis and promotes NSCLC progression via upregulating the PFKFB3\/PI3K-AKT pathway","volume":"37","author":"Zhu","year":"2026","journal-title":"Mamm Genome"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-025-10956-y","article-title":"Metabolic plasticity and cancer stem cell metabolism: Exploring the glycolysis-OXPHOS switch as a mechanism for resistance and tumorigenesis","volume":"21","author":"Keoh","year":"2025","journal-title":"Stem Cell Rev Rep"},{"key":"B31","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41572-024-00551-9","article-title":"Non-small-cell lung cancer","volume":"10","author":"Hendriks","year":"2024","journal-title":"Nat Rev Dis Primers"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiolchem.2025.108507","article-title":"A machine learning-based glycolysis and fatty acid metabolism-related prognostic signature is constructed and identified ACSL5 as a novel marker inhibiting the proliferation of breast cancer","volume":"119","author":"Liang","year":"2025","journal-title":"Comput Biol Chem"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1871582\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:39:00Z","timestamp":1784090340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1871582\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":32,"alternative-id":["10.3389\/fonc.2026.1871582"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1871582","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"article-number":"1871582"}}