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However, to date, there have been no systematic studies addressing its diagnostic, prognostic and immunological value across cancers. Here, we found that CDK12 was significantly upregulated in various types of cancers, and it expression increased with progression in ten cancer types, including breast cancer, cholangiocarcinoma and colon adenocarcinoma. Moreover, the ROC curves indicated that CDK12 showed diagnostic value in eight cancer types. High CDK12 expression was associated with poor prognosis in eight types of cancer, including low-grade glioma, mesothelioma, melanoma and pancreatic cancer. Furthermore, we conducted immunoassays to explore the exact mechanisms underlying CDK12-induced carcinogenesis, which revealed that increased expression of CDK12 allowed tumours to evade immune surveillance and upregulate immune checkpoint genes. Additionally, mutational studies have shown that amplification and missense mutations are the predominant mutational events affecting CDK12 across cancers. These findings establish CDK12 as a significant biological indicator of cancer diagnosis, prognosis, and immunotherapeutic targeting. Early surveillance and employment of CDK12 inhibitors, along with concomitant immunotherapy interventions, may enhance the clinical outcomes of cancer patients.<\/jats:p>","DOI":"10.1038\/s41598-024-56831-7","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T12:02:00Z","timestamp":1710849720000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["CDK12 is a potential biomarker for diagnosis, prognosis and immunomodulation in pan-cancer"],"prefix":"10.1038","volume":"14","author":[{"given":"Ke-Qi","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuo-Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Jie","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiangYun-Zi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"issue":"5","key":"56831_CR1","doi-asserted-by":"publisher","first-page":"034","DOI":"10.1093\/jnci\/djv034","volume":"107","author":"AA Dar","year":"2015","unstructured":"Dar, A. 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Targeting CDK12 for cancer therapy: Function, mechanism, and drug discovery.Cancer Res. 81(1), 18\u201326 (2021).","journal-title":"Cancer Res."},{"issue":"10","key":"56831_CR3","doi-asserted-by":"publisher","first-page":"e48058","DOI":"10.15252\/embr.201948058","volume":"20","author":"H-J Choi","year":"2019","unstructured":"Choi, H.-J. et al.CDK12 drives breast tumor initiation and trastuzumab resistance via WNT and IRS1-ErbB-PI3K signaling.EMBO Rep. 20(10), e48058 (2019).","journal-title":"EMBO Rep."},{"issue":"541","key":"56831_CR4","doi-asserted-by":"publisher","first-page":"8216","DOI":"10.1126\/scisignal.aam8216","volume":"11","author":"KL Henry","year":"2018","unstructured":"Henry, K. L. et al.CDK12-mediated transcriptional regulation of noncanonical NF-\u03baB components is essential for signaling.Sci. Signal. 11(541), 8216 (2018).","journal-title":"Sci. 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