{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:54:11Z","timestamp":1791010451651,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":274,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014418","name":"Harbin Medical University Cancer Hospital","doi-asserted-by":"publisher","award":["JJYQ2024-07"],"award-info":[{"award-number":["JJYQ2024-07"]}],"id":[{"id":"10.13039\/100014418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303616"],"award-info":[{"award-number":["82303616"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Genomics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lung adenocarcinoma (LUAD) is a major subtype of nonsmall cell lung cancer with substantial clinical heterogeneity. Nucleotide metabolism\u2010related genes may contribute to tumor progression and immune microenvironment remodeling, but their prognostic value in LUAD remains incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bulk transcriptomic and clinical data from TCGA\u2010LUAD and GEO datasets were analyzed to define nucleotide metabolism\u2010related molecular subtypes and construct a subtype\u2010derived prognostic signature from subtype\u2010associated differentially expressed genes. The TCGA\u2010LUAD cohort was randomly divided into a training cohort and an internal validation cohort at a ratio of 4:1. Univariate Cox regression and LASSO regression analyses were performed exclusively in the training cohort to construct the prognostic signature, which was subsequently evaluated in the internal validation cohort and the independent external bulk\u2010transcriptomic GSE30219 cohort. Consensus clustering, survival analysis, ROC analysis, immune infiltration analysis, mutation analysis, predicted drug sensitivity analysis, and exploratory single\u2010cell transcriptomic characterization were also performed. In vitro assays were used to evaluate the functional relevance of IRX5 in A549 LUAD cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 152 subtype\u2010associated differentially expressed genes were identified from pairwise comparisons among the three nucleotide metabolism\u2010related molecular subtypes, and a nine\u2010gene subtype\u2010derived prognostic signature consisting of SEMA3C, PTTG1, BARX1, CDCA5, TGFBI, MKI67, TSPAN7, GADD45G, and IRX5 was constructed. The signature stratified LUAD patients into high\u2010 and low\u2010risk groups with distinct overall survival and remained an independent prognostic factor. The risk score was associated with TP53 mutation frequency, immune cell infiltration patterns, cytokine\u2010 and exhaustion\u2010related scores, and predicted IC50 values for several anticancer agents. Single\u2010cell analysis revealed cell\u2010type\u2013specific expression patterns of signature genes and potential intercellular communication features in the LUAD microenvironment. Functionally, IRX5 knockdown inhibited proliferation, migration, and invasion, promoted apoptosis, and induced G0\/G1 cell\u2010cycle arrest in A549 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identified a subtype\u2010derived prognostic signature based on nucleotide metabolism\u2010related molecular classification with potential value for LUAD risk stratification and provided exploratory evidence linking signature genes to tumor immune features and cellular phenotypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijog\/4944325","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:51:38Z","timestamp":1791010298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Novel Subtype\u2010Derived Prognostic Signature Based on Nucleotide Metabolism\u2010Related Molecular Classification for Predicting Lung Adenocarcinoma Prognosis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2257-7529","authenticated-orcid":false,"given":"Yue","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Harbin Medical University Cancer Hospital  Harbin Heilongjiang China  hrbmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Clinic Heilongjiang Provincial Hospital  Harbin Heilongjiang China  hewiki.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7533-5953","authenticated-orcid":false,"given":"Lin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Harbin Medical University Cancer Hospital  Harbin Heilongjiang China  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