{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:58:08Z","timestamp":1781643488164,"version":"3.54.5"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0525600"],"award-info":[{"award-number":["2024ZD0525600"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82372753"],"award-info":[{"award-number":["82372753"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Tianjin Key Medical Discipline (Specialty) Construction Project","award":["TJYXZDXK-3-009B"],"award-info":[{"award-number":["TJYXZDXK-3-009B"]}]},{"name":"Tianjin Education Commission Research Program Project","award":["2023YXZD05"],"award-info":[{"award-number":["2023YXZD05"]}]},{"name":"Tianjin Municipal Science and Technology Project","award":["23ZYCGSN00960"],"award-info":[{"award-number":["23ZYCGSN00960"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Cell Int"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Backgrounds<\/jats:title>\n                    <jats:p>Neoadjuvant chemoradiation (nCRT) is a standard treatment for rectal carcinoma that reduces tumor size and local recurrence while improving the rate of sphincter preservation. However, many patients remain insensitive to nCRT, with some exhibiting tumor progression. To date, there is still a lack of clinically available prognostic models to differentiate the sensitivity of patients with rectal carcinoma to nCRT. This study aimed to develop a genetic predictive model that predicts the effectiveness of nCRT in patients with rectal carcinoma, offering guidance for future treatments and studies on the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Based on the NCBI GEO database datasets, key hub genes affecting the efficacy of neoadjuvant chemoradiotherapy in rectal carcinoma were identified using WCGNA. Subsequently, a consistency analysis of 101 model combinations constructed using ten different machine learning algorithms was performed in two independent cohorts, and a prognostic model (chemoradiation resistance score, CRTR score) was developed and validated. Moreover, the clinical applicability of CRTR in immunotherapy and drug selection was investigated using multi-omics analysis and public databases. Finally, the effect of KIF14 on the radiosensitivity of rectal carcinoma cells was studied using in vitro experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The CRTR model was composed of 13 genes impacting nCRT sensitivity, whereas six genes (KIF4, DBF4, UBL4A, SLC10A3, PRRG4, and PAPSS2) acted as protective factors and seven (BMS1, DSC2, PROM2, MNAT1, PPID, SMPDL3B, and TNFRSF14) served as risk factors. The CRTR model showed a significant negative correlation with the prognosis of patients with rectal carcinoma undergoing nCRT. Furthermore, patients with higher CRTR values displayed an increased potential to benefit from immunotherapy. Drug sensitivity analysis indicated that aurora kinase inhibitors, telomerase inhibitors, JAK1 inhibitors, and others may enhance the efficacy of nCRT. Finally, we identified KIF14 as the gene that contributed the most to the model and performed preliminary validation. Radiation significantly upregulated the expression of KIF14, and overexpression of KIF14 increased the radiosensitivity of rectal carcinoma cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The CRTR score, based on 13 genes, was able to predict the prognosis of patients with rectal carcinoma undergoing neoadjuvant chemoradiotherapy and demonstrated immense potential in providing personalized risk assessments and recommendations for targeted immunotherapy. The core gene, KIF14, in the CRTR model may serve as a potential predictive biomarker of radiosensitivity in rectal carcinioma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12935-026-04256-9","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T14:54:58Z","timestamp":1774104898000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A 13-gene prognostic model developed using machine learning to predict the response to neoadjuvant chemoradiotherapy in rectal carcinoma"],"prefix":"10.1186","volume":"26","author":[{"given":"Zhanhua","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxing","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaonan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinpu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqian","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"issue":"1","key":"4256_CR1","first-page":"12","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12\u201349.","journal-title":"CA Cancer J Clin"},{"issue":"6","key":"4256_CR2","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/s41575-024-00900-9","volume":"21","author":"Y Kagawa","year":"2024","unstructured":"Kagawa Y, et al. Future direction of total neoadjuvant therapy for locally advanced rectal cancer. Nat Rev Gastroenterol Hepatol. 2024;21(6):444\u201355.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"4256_CR3","doi-asserted-by":"publisher","unstructured":"Aaron J. Scott et al. Management of Locally Advanced Rectal Cancer: ASCO Guideline. J Clin Oncol 42, 3355-3375(2024). https:\/\/doi.org\/10.1200\/JCO.24.01160","DOI":"10.1200\/JCO.24.01160"},{"issue":"24","key":"4256_CR4","doi-asserted-by":"publisher","first-page":"4025","DOI":"10.1200\/JCO.22.02166","volume":"41","author":"R Ruppert","year":"2023","unstructured":"Ruppert R, et al. Risk-Adapted Neoadjuvant Chemoradiotherapy in Rectal Cancer: Final Report of the OCUM Study. J Clin Oncol. 2023;41(24):4025\u201334.","journal-title":"J Clin Oncol"},{"issue":"15","key":"4256_CR5","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1200\/JCO.2011.39.7901","volume":"30","author":"IJ Park","year":"2012","unstructured":"Park IJ, et al. Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol. 2012;30(15):1770\u20136.","journal-title":"J Clin Oncol"},{"key":"4256_CR6","doi-asserted-by":"publisher","first-page":"102796","DOI":"10.1016\/j.ctrv.2024.102796","volume":"129","author":"J Socha","year":"2024","unstructured":"Socha J, Glynne-Jones R, Bujko K. Oncological risks associated with the planned watch-and-wait strategy using total neoadjuvant treatment for rectal cancer: A narrative review. Cancer Treat Rev. 2024;129:102796.","journal-title":"Cancer Treat Rev"},{"issue":"8","key":"4256_CR7","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/j.annonc.2021.03.206","volume":"32","author":"A Grothey","year":"2021","unstructured":"Grothey A, Fakih M, Tabernero J. Management of BRAF-mutant metastatic colorectal cancer: a review of treatment options and evidence-based guidelines. Ann Oncol. 2021;32(8):959\u201367.","journal-title":"Ann Oncol"},{"issue":"1","key":"4256_CR8","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s12943-021-01441-4","volume":"20","author":"G Zhu","year":"2021","unstructured":"Zhu G, et al. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer. Mol Cancer. 2021;20(1):143.","journal-title":"Mol Cancer"},{"issue":"25","key":"4256_CR9","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1056\/NEJMoa2201445","volume":"386","author":"A Cercek","year":"2022","unstructured":"Cercek A, et al. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022;386(25):2363\u201376.","journal-title":"N Engl J Med"},{"issue":"3","key":"4256_CR10","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/ng.3214","volume":"47","author":"A Sottoriva","year":"2015","unstructured":"Sottoriva A, et al. A Big Bang model of human colorectal tumor growth. Nat Genet. 2015;47(3):209\u201316.","journal-title":"Nat Genet"},{"key":"4256_CR11","doi-asserted-by":"publisher","first-page":"105228","DOI":"10.1016\/j.ebiom.2024.105228","volume":"106","author":"E Domingo","year":"2024","unstructured":"Domingo E, et al. Identification and validation of a machine learning model of complete response to radiation in rectal cancer reveals immune infiltrate and TGFbeta as key predictors. EBioMedicine. 2024;106:105228.","journal-title":"EBioMedicine"},{"issue":"19","key":"4256_CR12","doi-asserted-by":"publisher","first-page":"4461","DOI":"10.1158\/1078-0432.CCR-14-2413","volume":"21","author":"TM Kim","year":"2015","unstructured":"Kim TM, et al. Subclonal Genomic Architectures of Primary and Metastatic Colorectal Cancer Based on Intratumoral Genetic Heterogeneity. Clin Cancer Res. 2015;21(19):4461\u201372.","journal-title":"Clin Cancer Res"},{"issue":"7","key":"4256_CR13","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/s41575-020-0275-y","volume":"17","author":"DS Keller","year":"2020","unstructured":"Keller DS, et al. The multidisciplinary management of rectal cancer. Nat Rev Gastroenterol Hepatol. 2020;17(7):414\u201329.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"7","key":"4256_CR14","doi-asserted-by":"publisher","first-page":"3370","DOI":"10.1158\/0008-5472.CAN-05-3834","volume":"66","author":"T Watanabe","year":"2006","unstructured":"Watanabe T, et al. Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles. Cancer Res. 2006;66(7):3370\u20134.","journal-title":"Cancer Res"},{"issue":"8","key":"4256_CR15","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1080\/15384047.2015.1046652","volume":"16","author":"M Agostini","year":"2015","unstructured":"Agostini M, et al. A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients. Cancer Biol Ther. 2015;16(8):1160\u201371.","journal-title":"Cancer Biol Ther"},{"issue":"4","key":"4256_CR16","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/j.ijrobp.2010.06.023","volume":"78","author":"M Spitzner","year":"2010","unstructured":"Spitzner M, et al. A gene expression signature for chemoradiosensitivity of colorectal cancer cells. Int J Radiat Oncol Biol Phys. 2010;78(4):1184\u201392.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"3","key":"4256_CR17","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1002\/gcc.22512","volume":"57","author":"Y Hu","year":"2018","unstructured":"Hu Y, et al. Colorectal cancer susceptibility loci as predictive markers of rectal cancer prognosis after surgery. Genes Chromosomes Cancer. 2018;57(3):140\u20139.","journal-title":"Genes Chromosomes Cancer"},{"issue":"8","key":"4256_CR18","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1038\/bjc.2015.93","volume":"112","author":"M Verstraete","year":"2015","unstructured":"Verstraete M, et al. Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial. Br J Cancer. 2015;112(8):1314\u201325.","journal-title":"Br J Cancer"},{"key":"4256_CR19","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"4256_CR20","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1038\/s41467-022-28421-6","volume":"13","author":"Z Liu","year":"2022","unstructured":"Liu Z, et al. Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer. Nat Commun. 2022;13(1):816.","journal-title":"Nat Commun"},{"issue":"3","key":"4256_CR21","first-page":"100141","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu T, et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innov (Camb). 2021;2(3):100141.","journal-title":"Innov (Camb)"},{"key":"4256_CR22","doi-asserted-by":"publisher","first-page":"1100481","DOI":"10.3389\/fonc.2022.1100481","volume":"12","author":"H Qin","year":"2022","unstructured":"Qin H, et al. Prognostic risk analysis related to radioresistance genes in colorectal cancer. Front Oncol. 2022;12:1100481.","journal-title":"Front Oncol"},{"key":"4256_CR23","doi-asserted-by":"publisher","first-page":"216641","DOI":"10.1016\/j.canlet.2024.216641","volume":"589","author":"Y Liu","year":"2024","unstructured":"Liu Y, et al. A deep neural network predictor to predict the sensitivity of neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Cancer Lett. 2024;589:216641.","journal-title":"Cancer Lett"},{"issue":"5","key":"4256_CR24","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nrc.2018.6","volume":"18","author":"W Ngwa","year":"2018","unstructured":"Ngwa W, et al. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer. 2018;18(5):313\u201322.","journal-title":"Nat Rev Cancer"},{"issue":"8","key":"4256_CR25","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1158\/0008-5472.CAN-20-4009","volume":"81","author":"B Zhang","year":"2021","unstructured":"Zhang B, et al. Chr20q Amplification Defines a Distinct Molecular Subtype of Microsatellite Stable Colorectal Cancer. Cancer Res. 2021;81(8):1977\u201387.","journal-title":"Cancer Res"},{"issue":"21","key":"4256_CR26","doi-asserted-by":"publisher","first-page":"e2206370","DOI":"10.1002\/adma.202206370","volume":"35","author":"W Zhen","year":"2023","unstructured":"Zhen W, Weichselbaum RR, Lin W. Nanoparticle-Mediated Radiotherapy Remodels the Tumor Microenvironment to Enhance Antitumor Efficacy. Adv Mater. 2023;35(21):e2206370.","journal-title":"Adv Mater"},{"issue":"Pt 2","key":"4256_CR27","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.semcancer.2022.04.003","volume":"86","author":"M Charpentier","year":"2022","unstructured":"Charpentier M, et al. Radiation therapy-induced remodeling of the tumor immune microenvironment. Semin Cancer Biol. 2022;86(Pt 2):737\u201347.","journal-title":"Semin Cancer Biol"},{"issue":"11","key":"4256_CR28","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1038\/nm.3967","volume":"21","author":"J Guinney","year":"2015","unstructured":"Guinney J, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350\u20136.","journal-title":"Nat Med"},{"issue":"4","key":"4256_CR29","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.ijrobp.2019.08.009","volume":"105","author":"X Ding","year":"2019","unstructured":"Ding X, et al. BIBR1532, a Selective Telomerase Inhibitor, Enhances Radiosensitivity of Non-Small Cell Lung Cancer Through Increasing Telomere Dysfunction and ATM\/CHK1 Inhibition. Int J Radiat Oncol Biol Phys. 2019;105(4):861\u201374.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"4256_CR30","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/s12931-019-1194-8","volume":"20","author":"N Liu","year":"2019","unstructured":"Liu N, et al. Inhibition of Aurora A enhances radiosensitivity in selected lung cancer cell lines. Respir Res. 2019;20(1):230.","journal-title":"Respir Res"},{"issue":"2","key":"4256_CR31","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1002\/ijc.28682","volume":"135","author":"Z-Z Lin","year":"2014","unstructured":"Lin Z-Z, et al. Radiosensitization by combining an aurora kinase inhibitor with radiotherapy in hepatocellular carcinoma through cell cycle interruption. Int J Cancer. 2014;135(2):492\u2013501.","journal-title":"Int J Cancer"},{"issue":"1","key":"4256_CR32","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s13046-019-1405-7","volume":"38","author":"SY Park","year":"2019","unstructured":"Park SY, et al. The JAK2\/STAT3\/CCND2 Axis promotes colorectal Cancer stem cell persistence and radioresistance. J Exp Clin Cancer Res. 2019;38(1):399.","journal-title":"J Exp Clin Cancer Res"},{"issue":"25","key":"4256_CR33","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.1038\/sj.onc.1201496","volume":"15","author":"W Mao","year":"1997","unstructured":"Mao W, et al. Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential. Oncogene. 1997;15(25):3083\u201390.","journal-title":"Oncogene"},{"issue":"14","key":"4256_CR34","doi-asserted-by":"publisher","first-page":"5931","DOI":"10.1158\/0008-5472.CAN-10-0694","volume":"70","author":"CJ Morrow","year":"2010","unstructured":"Morrow CJ, et al. Src family kinase inhibitor Saracatinib (AZD0530) impairs oxaliplatin uptake in colorectal cancer cells and blocks organic cation transporters. Cancer Res. 2010;70(14):5931\u201341.","journal-title":"Cancer Res"},{"issue":"5","key":"4256_CR35","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.cell.2007.11.011","volume":"131","author":"FA Barr","year":"2007","unstructured":"Barr FA, Gruneberg U. Cytokinesis: placing and making the final cut. Cell. 2007;131(5):847\u201360.","journal-title":"Cell"},{"issue":"1","key":"4256_CR36","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.bbadis.2018.10.039","volume":"1865","author":"Z Yang","year":"2019","unstructured":"Yang Z, et al. KIF14 promotes tumor progression and metastasis and is an independent predictor of poor prognosis in human gastric cancer. Biochim Biophys Acta Mol Basis Dis. 2019;1865(1):181\u201392.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"4256_CR37","doi-asserted-by":"publisher","first-page":"13241","DOI":"10.2147\/CMAR.S285367","volume":"12","author":"C Cheng","year":"2020","unstructured":"Cheng C, et al. KIF14 and KIF23 Promote Cell Proliferation and Chemoresistance in HCC Cells, and Predict Worse Prognosis of Patients with HCC. Cancer Manag Res. 2020;12:13241\u201357.","journal-title":"Cancer Manag Res"},{"issue":"2","key":"4256_CR38","first-page":"239","volume":"21","author":"HL Qiu","year":"2017","unstructured":"Qiu HL, et al. High expression of KIF14 is associated with poor prognosis in patients with epithelial ovarian cancer. Eur Rev Med Pharmacol Sci. 2017;21(2):239\u201345.","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"4256_CR39","doi-asserted-by":"publisher","unstructured":"Neska-D\u0142ugosz I et al. Prognostic Impact and Functional Annotations of KIF11 and KIF14 Expression in Patients with Colorectal Cancer. Int J Mol Sci, 2021. 22(18):9732. https:\/\/doi.org\/10.3390\/ijms22189732","DOI":"10.3390\/ijms22189732"},{"issue":"4","key":"4256_CR40","doi-asserted-by":"publisher","first-page":"e61664","DOI":"10.1371\/journal.pone.0061664","volume":"8","author":"PF Hung","year":"2013","unstructured":"Hung PF, et al. The motor protein KIF14 inhibits tumor growth and cancer metastasis in lung adenocarcinoma. PLoS ONE. 2013;8(4):e61664.","journal-title":"PLoS ONE"}],"container-title":["Cancer Cell International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12935-026-04256-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04256-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04256-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:38:45Z","timestamp":1781642325000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12935-026-04256-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,21]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4256"],"URL":"https:\/\/doi.org\/10.1186\/s12935-026-04256-9","relation":{},"ISSN":["1475-2867"],"issn-type":[{"value":"1475-2867","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,21]]},"assertion":[{"value":"31 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"181"}}