{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:05:20Z","timestamp":1784721920278,"version":"3.55.0"},"reference-count":19,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Lung adenocarcinoma (LUAD) is a clinically heterogeneous malignancy, and reliable prognostic biomarkers are still needed. Kinesin family members 4A and 4B (KIF4A and KIF4B) are mitosis-related motor proteins with potential functional overlap as paralogs. However, their coordinated prognostic significance in LUAD has not been systematically investigated. Materials and Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) were analyzed to evaluate the expression patterns, clinicopathologic associations, and prognostic significance of KIF4A and KIF4B in LUAD. Correlation analysis, Kaplan\u2013Meier survival analysis, and Cox proportional hazards regression analyses were performed. In addition, a combined paralog score and four-group expression model were evaluated. An independent LUAD cohort from the Gene Expression Omnibus (GEO; GSE81089) was analyzed for external validation. Results: KIF4A and KIF4B expression showed a strong positive correlation (r = 0.767, p &lt; 0.001), and both genes were positively correlated with EGFR, KRAS, BRAF, MKI67, and PCNA expression. High KIF4A expression was significantly associated with age, sex, smoking status, pathologic stage, N stage, and T stage, whereas high KIF4B expression was significantly associated with age and pathologic stage. Kaplan\u2013Meier analysis demonstrated that high expression of both KIF4A and KIF4B was associated with poorer overall survival. In Cox regression analyses, elevated expression of both genes remained significantly associated with unfavorable overall survival in univariable and multivariable models. However, when both genes were simultaneously included in the same Cox model, their individual prognostic effects were attenuated, suggesting substantial overlap in prognostic information. By contrast, the combined paralog score remained independently associated with poor overall survival. In four-group analysis, only patients with concurrent high expression of both KIF4A and KIF4B showed significantly worse overall survival compared with the low\/low group. External validation demonstrated generally consistent survival patterns, although the prognostic associations were attenuated after multivariable adjustment. Conclusions: KIF4A and KIF4B expression showed substantial prognostic overlap in LUAD, and their concurrent high expression was associated with poorer overall survival. These findings suggest that KIF4A\/KIF4B co-expression may serve as a candidate prognostic indicator that warrants validation in independent clinical cohorts and functional studies.<\/jats:p>","DOI":"10.3390\/medicina62071424","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:48:28Z","timestamp":1784717308000},"page":"1424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["KIF4A-KIF4B Paralog as a Prognostic Biomarker in Lung Adenocarcinoma"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9171-4058","authenticated-orcid":false,"given":"Hyun-Soo","family":"Park","sequence":"first","affiliation":[{"name":"Medical Course, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9437-5749","authenticated-orcid":false,"given":"Jun-Chae","family":"Lee","sequence":"additional","affiliation":[{"name":"Medical Course, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyowon","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-0720","authenticated-orcid":false,"given":"Jae-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","unstructured":"WHO Classification of Tumours Editorial Board (2021). Thoracic Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1097\/JTO.0000000000000630","article-title":"The 2015 World Health Organization classification of lung tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification","volume":"10","author":"Travis","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2014). Comprehensive molecular profiling of lung adenocarcinoma. Nature, 511, 543\u2013550.","DOI":"10.1038\/nature13385"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2012). Comprehensive genomic characterization of squamous cell lung cancers. Nature, 489, 519\u2013525.","DOI":"10.1038\/nature11404"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.cell.2012.08.029","article-title":"Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing","volume":"150","author":"Imielinski","year":"2012","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1126\/science.271.5256.1744","article-title":"Abnormal centrosome amplification in the absence of p53","volume":"271","author":"Fukasawa","year":"1996","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1083\/jcb.200303022","article-title":"The roles of microtubule-based motor proteins in mitosis: Comprehensive RNAi analysis in the Drosophila S2 cell line","volume":"162","author":"Goshima","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nrm2774","article-title":"Kinesin superfamily motor proteins and intracellular transport","volume":"10","author":"Hirokawa","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1101\/gr.984503","article-title":"Kinesin superfamily proteins (KIFs) in the mouse transcriptome","volume":"13","author":"Miki","year":"2003","journal-title":"Genome Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1083\/jcb.200401142","article-title":"Human chromokinesin KIF4A functions in chromosome condensation and segregation","volume":"166","author":"Mazumdar","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1091\/mbc.e05-02-0167","article-title":"Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis\/cytokinesis using RNA interference","volume":"16","author":"Zhu","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1083\/jcb.201202155","article-title":"Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase II\u03b1","volume":"199","author":"Samejima","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.cub.2011.04.019","article-title":"KIF4 regulates midzone length during cytokinesis","volume":"21","author":"Hu","year":"2011","journal-title":"Curr. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"BSR20203973","DOI":"10.1042\/BSR20203973","article-title":"Identification of KIF4A and its effect on the progression of lung adenocarcinoma based on the bioinformatics analysis","volume":"41","author":"Song","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44957","DOI":"10.1038\/s41598-025-29206-9","article-title":"Kinesin genes KIF4A, KIF20A and KIF11 as prognostic biomarkers in lung adenocarcinoma by integrative bioinformatic analysis and experimental validation","volume":"15","author":"Wang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000015482","article-title":"Assignment of the kinesin family member 4 genes (KIF4A and KIF4B) to human chromosome bands Xq13.1 and 5q33.1 by in situ hybridization","volume":"88","author":"Ha","year":"2000","journal-title":"Cytogenet. Cell Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1042\/BCJ20210140","article-title":"Regulation of the mitotic chromosome folding machines","volume":"479","author":"Dekker","year":"2022","journal-title":"Biochem. J."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/7\/1424\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:52:54Z","timestamp":1784721174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/7\/1424"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":19,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["medicina62071424"],"URL":"https:\/\/doi.org\/10.3390\/medicina62071424","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}