{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T08:08:59Z","timestamp":1779091739803,"version":"3.51.4"},"reference-count":25,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the Jinhua Science and Technology Program","award":["2022-4-086"],"award-info":[{"award-number":["2022-4-086"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cancer Control"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The prognostic value of cyclin-dependent kinase 5 (CDK5) was investigated in a cohort of patients with cetuximab-treated, chemotherapy-refractory, dual wild-type Rat Sarcoma and v-raf murine sarcoma viral oncogene homolog B1 (RAS\/BRAF) metastatic colorectal adenocarcinoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Immunohistochemistry (IHC) was used to retrospectively analyze the expression of CDK5 in metastatic colorectal adenocarcinoma tissue samples of 129 patients. All statistical computations were performed in R 4.0.5. Dichotomous clinicopathological variables were then cross-tabulated across CDK5 strata and compared with Pearson\u2019s \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      test. Cumulative survival probabilities were estimated via the Kaplan\u2013Meier estimator and contrasted with the log-rank test. Independent prognostic determinants were ascertained through Cox proportional-hazards.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      79 men and 50 women were enrolled in this study, with a median age 62.8 years. Among 129 specimens subjected to CDK5 IHC, 111 tumor cores yielded unequivocally evaluable results. 69 lesions were allocated to the low-to-intermediate expression tier (scores 0\u20132+), whereas 42 exhibited marked overexpression (score 3+). Elevated CDK5 immunoreactivity was shown to predict inferior progression-free survival (PFS) (7.0 versus 9.0 months;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.049) and a shortened cancer-specific survival (CSS) (27.8 vs 38.5 months;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.048). In addition, low-to-intermediate CDK5 expression remained independently associated with PFS (HR 0.544; 95 % CI 0.369\u20130.801;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.002) and CSS (HR 0.502; 95% CI: 0.329\u20130.766;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.001). CDK5 overexpression conferred a statistically significant detriment to PFS among patients harboring only extra-hepatic metastases (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.012), while within the hepatic-metastatic subset, no survival discrepancy was discernible between the high and low-to-intermediate expression cohorts (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.800).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Independent multivariable modelling identified elevated CDK5 as a robust predictor of both curtailed PFS and CSS. Intriguingly, this prognostic power appears to be contingent upon the site of disease: once the cancer metastasizes to the liver, the predictive signal of elevated CDK5 is abruptly extinguished.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10732748261453119","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:11:15Z","timestamp":1778865075000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Topography-dependent Prognostic Value of CDK5 in Cetuximab-Treated, RAS\/BRAF-wild-type Metastatic Colorectal Cancer: A Retrospective Tissue-Microarray Analysis"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4557-5989","authenticated-orcid":false,"given":"Qinghua","family":"Wang","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital, Zhejiang University School of Medicine"},{"name":"Zhejiang University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Hu","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingjing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3036-1056","authenticated-orcid":false,"given":"Jianfei","family":"Fu","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Yuan","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Zhejiang University School of Medicine"},{"name":"The Second Affiliated Hospital, Zhejiang University School of Medicine"},{"name":"Zhejiang Provincial Clinical Research Center for CANCER"},{"name":"Zhejiang University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327736"},{"key":"e_1_3_7_3_2","first-page":"E499","article-title":"Global Disparities in Colorectal Cancer: Unveiling the Present Landscape of Incidence and Mortality Rates, Analyzing Geographical Variances, and Assessing the Human Development Index","volume":"65","author":"Darmadi D","year":"2024","unstructured":"Darmadi D, Mohammadian-Hafshejani A, Kheiri S. Global Disparities in Colorectal Cancer: Unveiling the Present Landscape of Incidence and Mortality Rates, Analyzing Geographical Variances, and Assessing the Human Development Index. Journal of preventive medicine and hygiene. 2024;65:E499-e514.","journal-title":"Journal of preventive medicine and hygiene"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065588"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241411733"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12091534"},{"key":"e_1_3_7_7_2","first-page":"S95","article-title":"P-18 REMARRY and PURSUIT Trials: Liquid Biopsy-Guided Re-Challenge of Anti-Egfr Monoclonal Antibody for Patients with RAS\/BRAF V600E Wild-Type Metastatic Colorectal Cancer","volume":"31","author":"Nakajima H","year":"2020","unstructured":"Nakajima H, Kotani D, Oki E, et al. P-18 REMARRY and PURSUIT Trials: Liquid Biopsy-Guided Re-Challenge of Anti-Egfr Monoclonal Antibody for Patients with RAS\/BRAF V600E Wild-Type Metastatic Colorectal Cancer. The American journal of gastroenterology. 2020;31:S95-S.","journal-title":"The American journal of gastroenterology"},{"key":"e_1_3_7_8_2","doi-asserted-by":"crossref","unstructured":"Boussios S Ozturk MA Moschetta M et al. The Developing Story of Predictive Biomarkers in Colorectal Cancer. Journal of personalized medicine. 2019;9.","DOI":"10.3390\/jpm9010012"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3048"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1107"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805019"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/10732748231169396"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2014.07.013"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00010"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.333"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.76809"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9010128"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.545251"},{"key":"e_1_3_7_19_2","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1186\/s13046-019-1297-6","article-title":"CDK5-mediated Phosphorylation and Stabilization of TPX2 Promotes Hepatocellular Tumorigenesis","volume":"38","author":"Wang F","year":"2019","unstructured":"Wang F, Zhao W, Gao Y, et al. CDK5-mediated Phosphorylation and Stabilization of TPX2 Promotes Hepatocellular Tumorigenesis. Journal of experimental & clinical cancer research : CR. 2019;38:286.","journal-title":"Journal of experimental & clinical cancer research : CR"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13082038"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-340"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-023-11600-z"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2021.1902505"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01895-8"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13010101"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-025-02193-3"}],"container-title":["Cancer Control"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10732748261453119","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10732748261453119","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10732748261453119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T07:47:44Z","timestamp":1779090464000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10732748261453119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":25,"alternative-id":["10.1177\/10732748261453119"],"URL":"https:\/\/doi.org\/10.1177\/10732748261453119","relation":{"has-review":[{"id-type":"doi","id":"10.1177\/10732748261453119\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1177\/10732748261453119\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1177\/10732748261453119\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1177\/10732748261453119\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1177\/10732748261453119\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1177\/10732748261453119\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1177\/10732748261453119\/v2\/response1","asserted-by":"object"}]},"ISSN":["1073-2748","1526-2359"],"issn-type":[{"value":"1073-2748","type":"print"},{"value":"1526-2359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"article-number":"10732748261453119"}}