{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:04:49Z","timestamp":1784153089185,"version":"3.55.0"},"reference-count":62,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Kidney renal clear cell carcinoma (KIRC) is a highly aggressive and heterogeneous malignancy characterized by poor clinical outcomes and limited reliable prognostic biomarkers. This study performed a comprehensive bioinformatic analysis to evaluate the clinical and biological significance of threonine\u2013tyrosine kinase (TTK\/Mps1) in KIRC. Transcriptomic analyses demonstrated significant overexpression of TTK in tumor tissues, which was strongly associated with advanced stage, metastatic progression, and reduced patient survival. Multivariate regression confirmed TTK as an independent prognostic indicator with high diagnostic accuracy. Network and enrichment analyses revealed that TTK is embedded within a tightly connected mitotic regulatory module, primarily involving spindle assembly checkpoint signaling, G2\/M transition control, and chromosome segregation processes. Key co\u2010expressed genes included BUB1, CCNB1, CDK1, and CENPF, indicating a coordinated proliferative program. Pathway analysis further showed strong positive associations with oncogenic cell\u2010cycle signatures and negative correlations with metabolic pathways. Immune profiling indicated that elevated TTK expression correlates with increased immune infiltration and is associated with alterations in the tumor microenvironment. Collectively, these findings suggest that TTK is associated with prognosis and may serve as a potential biomarker in KIRC, with its therapeutic relevance requiring further investigation.<\/jats:p>","DOI":"10.1002\/mc.70132","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:30:14Z","timestamp":1779816614000},"page":"989-1005","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TTK Overexpression as a Prognostic Indicator and Immune Modulator in Kidney Renal Clear Cell Carcinoma"],"prefix":"10.1002","volume":"65","author":[{"given":"Anuradha","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Biology Indian Institute of Technology (Indian School of Mines) Dhanbad jharkhand India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-2224","authenticated-orcid":false,"given":"Naga Rajiv","family":"Lakkaniga","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Indian Institute of Technology (Indian School of Mines) Dhanbad jharkhand India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21590"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S521272"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2008.04.001"},{"issue":"4","key":"e_1_2_10_7_1","first-page":"245","article-title":"Clear Cell Renal Cell Carcinoma Ontogeny and Mechanisms of Lethality","volume":"17","author":"Jonasch E.","year":"2020","journal-title":"Nature Reviews Nephrology 2020 17:4"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.04.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18403"},{"issue":"4","key":"e_1_2_10_10_1","first-page":"152","article-title":"Systemic Therapy for Metastatic Renal\u2010Cell Carcinoma","volume":"376","author":"Tk C.","year":"2017","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4921"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203938"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.6140"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.79.2549"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061611-090435"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.26796"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2025.02.005"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202050257"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21994"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116504"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113776"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2017.02.030"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-0864"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.460"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-023-03192-2"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)49633-6"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04429-6"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112589"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4MD00003J"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.02.007"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2018.06.003"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-020-00359-2"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-024-03575-z"},{"issue":"1","key":"e_1_2_10_34_1","first-page":"17","article-title":"Tumor\u2010Initiating and Metastasis\u2010Initiating Cells of Clear\u2010Cell Renal Cell Carcinoma","volume":"32","author":"Pham D. 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