{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:21:42Z","timestamp":1773102102258,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minister of Science under \u201cthe Regional Initiative of Excellence Program\u201d","award":["NN402 452339"],"award-info":[{"award-number":["NN402 452339"]}]},{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"publisher","award":["NN402 452339"],"award-info":[{"award-number":["NN402 452339"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Warmia and Mazury in Olsztyn","award":["NN402 452339"],"award-info":[{"award-number":["NN402 452339"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Special AT-rich sequence-binding protein 2 (SATB2), as a nuclear matrix-associated protein and transcription factor engaged in chromatin remodeling and the regulation of gene expression, plays an important role in growth and development processes. SATB2 has been shown to have tissue-specific expression, also related to some cancers, including colorectal cancer (CRC). The aim of this study was to compare SATB2 gene expression in tumor and matched non-involved colorectal tissues obtained from CRC patients, and to investigate its association with clinicopathological and demographic parameters, as well as patients\u2019 overall survival. SATB2 mRNA levels in the tested tissues were assessed by quantitative polymerase chain reaction, while SATB2 protein expression was determined by immunohistochemistry. We found that the average levels of both SATB2 mRNA and protein were significantly lower in tumor specimens than in matched non-involved colon tissues. Moreover, SATB2 immunoreactivity was associated with patients\u2019 sex, tumor localization, and grade of differentiation. Lower immunoreactivity of SATB2 protein was noted in high-grade tumors, in women, and in tumors located in the cecum, ascending, and transverse colon. However, the results of the present study did not show an association between SATB2 expression levels and patients\u2019 overall survival. Our findings indicate the involvement of impaired SATB2 expression, significantly reduced in high-grading tumors, in the pathogenesis of CRC, while its sex- and localization-specificity should be further elucidated.<\/jats:p>","DOI":"10.3390\/ijms26052374","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T11:11:27Z","timestamp":1741259487000},"page":"2374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduced Expression of SATB2 in Colorectal Cancer and Its Association with Demographic and Clinicopathological Parameters"],"prefix":"10.3390","volume":"26","author":[{"given":"Anna Ewa","family":"Kowalczyk","sequence":"first","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"\u015aliwi\u0144ska-Jewsiewicka","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3537-4710","authenticated-orcid":false,"given":"Bart\u0142omiej Emil","family":"Krazi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4093-7386","authenticated-orcid":false,"given":"Aleksandra","family":"Piotrowska","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u0119drzej","family":"Grzegrz\u00f3\u0142ka","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janusz","family":"Godlewski","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Dzi\u0119giel","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-8166","authenticated-orcid":false,"given":"Zbigniew","family":"Kmie\u0107","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5114\/pg.2018.81072","article-title":"Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors","volume":"14","author":"Rawla","year":"2019","journal-title":"Gastroenterol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1136\/flgastro-2013-100329","article-title":"The molecular genetics of colorectal cancer","volume":"5","author":"Ewing","year":"2014","journal-title":"Frontline Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.gendis.2020.10.003","article-title":"SATB2: A versatile transcriptional regulator of craniofacial and skeleton development, neurogenesis and tumorigenesis, and its applications in regenerative medicine","volume":"9","author":"Huang","year":"2020","journal-title":"Genes Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"451","DOI":"10.5858\/arpa.2021-0317-OA","article-title":"SATB2 Expression in Human Tumors: A Tissue Microarray Study on More Than 15\u2009000 Tumors","volume":"147","author":"Dum","year":"2023","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1101\/gad.1153003","article-title":"SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression","volume":"17","author":"Dobreva","year":"2003","journal-title":"Genes Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1038\/onc.2014.289","article-title":"SATB2 enhances migration and invasion in osteosarcoma by regulating genes involved in cytoskeletal organization","volume":"34","author":"Seong","year":"2015","journal-title":"Oncogene"},{"key":"ref_8","first-page":"4516","article-title":"Metformin reduces SATB2-mediated osteosarcoma stem cell-like phenotype and tumor growth via inhibition of N-cadherin\/NF-kB signaling","volume":"21","author":"Xu","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7999","DOI":"10.1111\/jcmm.14652","article-title":"Higher expression of SATB2 in hepatocellular carcinoma of African Americans determines more aggressive phenotypes than those of Caucasian Americans","volume":"23","author":"Yu","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9457","DOI":"10.18632\/oncotarget.3265","article-title":"miR-211 suppresses hepatocellular carcinoma by downregulating SATB2","volume":"6","author":"Jiang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1475-2867-9-18","article-title":"The mRNA expression of SATB1 and SATB2 in human breast cancer","volume":"9","author":"Patani","year":"2009","journal-title":"Cancer Cell Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.scr.2017.01.011","article-title":"Cellular transformation of human mammary epithelial cells by SATB2","volume":"19","author":"Yu","year":"2017","journal-title":"Stem Cell Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/embor.2010.125","article-title":"SATB2 augments \u0394Np63\u03b1 in head and neck squamous cell carcinoma","volume":"11","author":"Chung","year":"2010","journal-title":"EMBO Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liu, T.R., Xu, L.H., Yang, A.K., Zhong, Q., Song, M., Li, M.Z., Hu, L.J., Chen, F.J., Hu, Z.D., and Han, P. (2012). Decreased expression of SATB2: A novel independent prognostic marker of worse outcome in laryngeal carcinoma patients. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040704"},{"key":"ref_15","first-page":"423","article-title":"Prognostic value of SATB2 expression in patients with esophageal squamous cell carcinoma","volume":"8","author":"Geng","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.lungcan.2016.05.032","article-title":"Downregulation of SATB2 is critical for induction of epithelial-to-mesenchymal transition and invasion of NSCLC cells","volume":"98","author":"Kucuksayan","year":"2016","journal-title":"Lung Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/cjp2.131","article-title":"A COEUR cohort study of SATB2 expression and its prognostic value in ovarian endometrioid carcinoma","volume":"5","author":"Meunier","year":"2019","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_18","first-page":"839","article-title":"Decreased Expression of SATB2 Associates with Tumor Growth and Predicts Worse Outcome in Patients with Clear Cell Renal Cell Carcinoma","volume":"38","author":"Kowalczyk","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yu, W., Ma, Y., Shankar, S., and Srivastava, R.K. (2017). SATB2\/\u03b2-catenin\/TCF-LEF pathway induces cellular transformation by generating cancer stem cells in colorectal cancer. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-05458-y"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100975","DOI":"10.18632\/oncotarget.10900","article-title":"miR-449a inhibits colorectal cancer progression by targeting SATB2","volume":"8","author":"Sun","year":"2016","journal-title":"Oncotarget"},{"key":"ref_21","first-page":"4847","article-title":"miR-3666 suppresses cellular proliferation and invasion in colorectal cancer by targeting SATB2","volume":"18","author":"Yang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/path.2575","article-title":"Down-regulated expression of SATB2 is associated with metastasis and poor prognosis in colorectal cancer","volume":"219","author":"Wang","year":"2009","journal-title":"J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/bjc.2012.34","article-title":"A cohort study of the prognostic and treatment predictive value of SATB2 expression in colorectal cancer","volume":"106","author":"Eberhard","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e12455","DOI":"10.1111\/cpr.12455","article-title":"SATB2 targeted by methylated miR-34c-5p suppresses proliferation and metastasis attenuating the epithelial-mesenchymal transition in colorectal cancer","volume":"51","author":"Gu","year":"2018","journal-title":"Cell Prolif."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1111\/febs.13227","article-title":"SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5\/ERK5 signaling","volume":"282","author":"Mansour","year":"2015","journal-title":"FEBS J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8528","DOI":"10.3748\/wjg.v22.i38.8528","article-title":"Special AT-rich sequence-binding protein 2 acts as a negative regulator of stemness in colorectal cancer cells","volume":"22","author":"Li","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4993","DOI":"10.18632\/oncotarget.6651","article-title":"SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer","volume":"7","author":"Mansour","year":"2016","journal-title":"Oncotarget"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hrudka, J., Mat\u011bj, R., Nikov, A., Tomyak, I., Fi\u0161erov\u00e1, H., Jel\u00ednkov\u00e1, K., and Waldauf, P. (2022). Loss of SATB2 expression correlates with cytokeratin 7 and PD-L1 tumor cell positivity and aggressiveness in colorectal cancer. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22685-0"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1080\/0284186X.2019.1691258","article-title":"Metastatic colorectal carcinomas with high SATB2 expression are associated with better prognosis and response to chemotherapy: A population-based Scandinavian study","volume":"59","author":"Mezheyeuski","year":"2020","journal-title":"Acta Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00795-023-00366-9","article-title":"Loss of SATB2 and CDX2 expression is associated with DNA mismatch repair protein deficiency and BRAF mutation in colorectal cancer","volume":"57","author":"Li","year":"2024","journal-title":"Med. Mol. Morphol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/s41379-019-0265-1","article-title":"SATB2 and CDX2 are prognostic biomarkers in DNA mismatch repair protein deficient colon cancer","volume":"32","author":"Ma","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Schmitt, M., Silva, M., Konukiewitz, B., Lang, C., Steiger, K., Halfter, K., Engel, J., Jank, P., Pfarr, N., and Wilhelm, D. (2021). Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups. Cancers, 13.","DOI":"10.3390\/cancers13246177"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151731","DOI":"10.1016\/j.anndiagpath.2021.151731","article-title":"Immunohistochemical expression and significance of SATB2 protein in colorectal cancer","volume":"52","author":"Adamkov","year":"2021","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/gutjnl-2015-310912","article-title":"Global patterns and trends in colorectal cancer incidence and mortality","volume":"66","author":"Arnold","year":"2017","journal-title":"Gut"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6094","DOI":"10.1038\/s41467-021-26234-7","article-title":"Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis","volume":"12","author":"Pradhan","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1097\/PAS.0b013e31821c3dae","article-title":"SATB2 in combination with cytokeratin 20 identifies over 95% of all colorectal carcinomas","volume":"35","author":"Magnusson","year":"2011","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1093\/carcin\/bgu322","article-title":"SATB1 and 2 in colorectal cancer","volume":"36","author":"Brocato","year":"2015","journal-title":"Carcinogenesis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1309\/AJCPWW2URZ9JKQJU","article-title":"The role of SATB2 as a diagnostic marker for tumors of colorectal origin: Results of a pathology-based clinical prospective study","volume":"141","author":"Dragomir","year":"2014","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.5858\/arpa.2013-0452-OA","article-title":"Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine","volume":"138","author":"Lin","year":"2014","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"152302","DOI":"10.1016\/j.anndiagpath.2024.152302","article-title":"Meta-analysis of SATB2 immunohistochemical expression in colorectal cancer versus primary ovarian mucinous neoplasms","volume":"71","author":"Maguire","year":"2024","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/PAI.0000000000001216","article-title":"Use of SATB2 and CDX2 Immunohistochemistry to Characterize and Diagnose Colorectal Cancer","volume":"32","author":"Kato","year":"2024","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.5858\/arpa.2016-0243-RS","article-title":"SATB2 as an Immunohistochemical Marker for Colorectal Adenocarcinoma: A Concise Review of Benefits and Pitfalls","volume":"141","author":"Berg","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"221","DOI":"10.14740\/gr1015w","article-title":"SATB2 Shows Different Profiles Between Appendiceal Adenocarcinomas Ex Goblet Cell Carcinoids and Appendiceal\/Colorectal Conventional Adenocarcinomas: An Immunohistochemical Study With Comparison to CDX2","volume":"11","author":"Yang","year":"2018","journal-title":"Gastroenterol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1136\/jclinpath-2015-203588","article-title":"Value of SATB2 immunostaining in the distinction between small intestinal and colorectal adenocarcinomas","volume":"69","author":"Kim","year":"2016","journal-title":"J. Clin. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.3332\/ecancer.2022.1491","article-title":"Diagnostic accuracy of SATB2 in identifying primary and metastatic colorectal carcinoma: A comparative immunohistochemical study","volume":"16","author":"Elnady","year":"2022","journal-title":"Ecancermedicalscience"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"152430","DOI":"10.1016\/j.prp.2019.04.022","article-title":"Significance of SATB2 expression in colon cancer and its differential diagnosis in digestive tract adenocarcinoma and ovarian primary and metastatic carcinoma","volume":"215","author":"Liu","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yang, M.H., Yu, J., Chen, N., Wang, X.Y., Liu, X.Y., Wang, S., and Ding, Y.Q. (2013). Elevated microRNA-31 expression regulates colorectal cancer progression by repressing its target gene SATB2. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0085353"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/1479-5876-12-109","article-title":"microRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis","volume":"12","author":"Yang","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1039\/c2mt20074k","article-title":"Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer","volume":"4","author":"Clancy","year":"2012","journal-title":"Metallomics"},{"key":"ref_51","first-page":"115","article-title":"Immunohistochemical expression of SATB2 and clinicopathological correlation in colorectal adenocarcinoma","volume":"10","author":"Eldeeb","year":"2022","journal-title":"Merit Res. J. Med. Med. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/S0140-6736(19)32319-0","article-title":"Colorectal cancer","volume":"394","author":"Dekker","year":"2019","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"951","DOI":"10.3892\/ijo.2015.3067","article-title":"Altered expression of the PLAGL1 (ZAC1\/LOT1) gene in colorectal cancer: Correlations to the clinicopathological parameters","volume":"47","author":"Kowalczyk","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4441","DOI":"10.1007\/s13277-015-3084-0","article-title":"Divergent expression patterns of SATB1 mRNA and SATB1 protein in colorectal cancer and normal tissues","volume":"36","author":"Kowalczyk","year":"2015","journal-title":"Tumour Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2374\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:48:35Z","timestamp":1760028515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,6]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26052374"],"URL":"https:\/\/doi.org\/10.3390\/ijms26052374","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,6]]}}}