{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:55:21Z","timestamp":1792742121859,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hunan Province,China","doi-asserted-by":"crossref","award":["2025JJ70052"],"award-info":[{"award-number":["2025JJ70052"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2508085QH310"],"award-info":[{"award-number":["2508085QH310"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304794"],"award-info":[{"award-number":["82304794"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2022JJ40833"],"award-info":[{"award-number":["2022JJ40833"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ6728"],"award-info":[{"award-number":["2024JJ6728"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"publisher","award":["Z2023100"],"award-info":[{"award-number":["Z2023100"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"DOI":"10.1007\/s10238-025-01917-3","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T02:30:01Z","timestamp":1763433001000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["CD2AP is a disulfidptosis modulator and prognostic biomarker in hepatocellular carcinoma"],"prefix":"10.1007","volume":"26","author":[{"given":"Yingzheng","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingbin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenliang","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"1917_CR1","first-page":"7","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7\u201333.","journal-title":"CA Cancer J Clin"},{"key":"1917_CR2","doi-asserted-by":"publisher","first-page":"308","DOI":"10.2478\/jtim-2022-0068","volume":"10","author":"K Moller","year":"2022","unstructured":"Moller K, Safai Zadeh E, Gorg C, Dong Y, Cui X, Lim A, et al. Focal liver lesions other than hepatocellular carcinoma in cirrhosis: diagnostic challenges. J Transl Int Med. 2022;10:308\u201327.","journal-title":"J Transl Int Med"},{"key":"1917_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115801","author":"K Oura","year":"2021","unstructured":"Oura K, Morishita A, Tani J, Masaki T. Tumor immune microenvironment and immunosuppressive therapy in hepatocellular carcinoma: a review. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms22115801.","journal-title":"Int J Mol Sci"},{"key":"1917_CR4","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/S0140-6736(22)01200-4","volume":"400","author":"A Vogel","year":"2022","unstructured":"Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400:1345\u201362.","journal-title":"Lancet"},{"key":"1917_CR5","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1093\/jnci\/djad213","volume":"116","author":"S Beltr\u00e1n Ponce","year":"2024","unstructured":"Beltr\u00e1n Ponce S, Gokun Y, Douglass F, Dawson L, Miller E, Thomas CR Jr, et al. Disparities in outcomes and access to therapy options in hepatocellular carcinoma. J Natl Cancer Inst. 2024;116:264\u201374.","journal-title":"J Natl Cancer Inst"},{"key":"1917_CR6","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1080\/17474124.2018.1453806","volume":"12","author":"G Zhang","year":"2018","unstructured":"Zhang G, Li R, Deng Y, Zhao L. Conditional survival of patients with hepatocellular carcinoma: results from the surveillance, epidemiology, and end results registry. Expert Rev Gastroenterol Hepatol. 2018;12:515\u201323.","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"1917_CR7","doi-asserted-by":"publisher","first-page":"e555","DOI":"10.1016\/S2214-109X(18)30127-X","volume":"6","author":"H Zeng","year":"2018","unstructured":"Zeng H, Chen W, Zheng R, Zhang S, Ji JS, Zou X, et al. Changing cancer survival in China during 2003\u201315: a pooled analysis of 17 population-based cancer registries. Lancet Glob Health. 2018;6:e555\u201367.","journal-title":"Lancet Glob Health"},{"key":"1917_CR8","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1515\/jtim-2025-0004","volume":"13","author":"Z Guo","year":"2025","unstructured":"Guo Z, Liu Y, Chen D, Sun Y, Li D, Meng Y, et al. Targeting regulated cell death: apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity. J Transl Int Med. 2025;13:10\u201332.","journal-title":"J Transl Int Med"},{"key":"1917_CR9","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41556-023-01091-2","volume":"25","author":"X Liu","year":"2023","unstructured":"Liu X, Nie L, Zhang Y, Yan Y, Wang C, Colic M, et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nat Cell Biol. 2023;25:404\u201314.","journal-title":"Nat Cell Biol"},{"key":"1917_CR10","doi-asserted-by":"publisher","first-page":"3673","DOI":"10.1038\/s41467-023-39401-9","volume":"14","author":"Y Yan","year":"2023","unstructured":"Yan Y, Teng H, Hang Q, Kondiparthi L, Lei G, Horbath A, et al. Slc7a11 expression level dictates differential responses to oxidative stress in cancer cells. Nat Commun. 2023;14:3673.","journal-title":"Nat Commun"},{"key":"1917_CR11","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13046-023-02675-4","volume":"42","author":"P Zheng","year":"2023","unstructured":"Zheng P, Zhou C, Ding Y, Duan S. Disulfidptosis: a new target for metabolic cancer therapy. J Exp Clin Cancer Res. 2023;42:103.","journal-title":"J Exp Clin Cancer Res"},{"key":"1917_CR12","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.tcb.2023.07.009","volume":"34","author":"X Liu","year":"2024","unstructured":"Liu X, Zhuang L, Gan B. Disulfidptosis: disulfide stress-induced cell death. Trends Cell Biol. 2024;34:327\u201337.","journal-title":"Trends Cell Biol"},{"key":"1917_CR13","doi-asserted-by":"publisher","first-page":"4588","DOI":"10.1242\/jcs.175075","volume":"128","author":"TA Tolvanen","year":"2015","unstructured":"Tolvanen TA, Dash SN, Polianskyte-Prause Z, Dumont V, Lehtonen S. Lack of CD2AP disrupts Glut4 trafficking and attenuates glucose uptake in podocytes. J Cell Sci. 2015;128:4588\u2013600.","journal-title":"J Cell Sci"},{"key":"1917_CR14","doi-asserted-by":"publisher","first-page":"901","DOI":"10.14336\/AD.2018.1025","volume":"10","author":"QQ Tao","year":"2019","unstructured":"Tao QQ, Chen YC, Wu ZY. The role of CD2AP in the pathogenesis of Alzheimer\u2019s disease. Aging Dis. 2019;10:901\u20137.","journal-title":"Aging Dis"},{"key":"1917_CR15","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201812087","author":"Y Wang","year":"2020","unstructured":"Wang Y, Brieher WM. CD2AP links actin to PI3 kinase activity to extend epithelial cell height and constrain cell area. J Cell Biol. 2020. https:\/\/doi.org\/10.1083\/jcb.201812087.","journal-title":"J Cell Biol"},{"key":"1917_CR16","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/s41419-022-04887-6","volume":"13","author":"L Yang","year":"2022","unstructured":"Yang L, Tan W, Wei Y, Xie Z, Li W, Ma X, et al. Circlifr suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3\u03b2\/\u03b2-catenin signaling pathway. Cell Death Dis. 2022;13:464.","journal-title":"Cell Death Dis"},{"key":"1917_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217470","volume":"612","author":"L Yang","year":"2025","unstructured":"Yang L, Tan W, Wang M, Wei Y, Xie Z, Wang Q, et al. Circccny enhances lenvatinib sensitivity and suppresses immune evasion in hepatocellular carcinoma by serving as a scaffold for SMURF1 mediated HSP60 degradation. Cancer Lett. 2025;612:217470.","journal-title":"Cancer Lett"},{"key":"1917_CR18","doi-asserted-by":"publisher","first-page":"5872","DOI":"10.1038\/s41467-021-26180-4","volume":"12","author":"Z Zhang","year":"2021","unstructured":"Zhang Z, Li X, Yang F, Chen C, Liu P, Ren Y, et al. DHHC9-mediated GLUT1 S-palmitoylation promotes glioblastoma glycolysis and tumorigenesis. Nat Commun. 2021;12:5872.","journal-title":"Nat Commun"},{"key":"1917_CR19","doi-asserted-by":"publisher","DOI":"10.34133\/research.0080","volume":"6","author":"X Ji","year":"2023","unstructured":"Ji X, Tian X, Feng S, Zhang L, Wang J, Guo R, et al. Intermittent F-actin perturbations by magnetic fields inhibit breast cancer metastasis. Research. 2023;6:0080.","journal-title":"Research"},{"key":"1917_CR20","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1038\/s41591-018-0136-1","volume":"24","author":"P Jiang","year":"2018","unstructured":"Jiang P, Gu S, Pan D, Fu J, Sahu A, Hu X, et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat Med. 2018;24:1550\u20138.","journal-title":"Nat Med"},{"key":"1917_CR21","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1007\/s00428-004-1166-2","volume":"446","author":"J Tienari","year":"2005","unstructured":"Tienari J, Lehtonen S, Lehtonen E. CD2-associated protein in human urogenital system and in adult kidney tumours. Virchows Arch. 2005;446:394\u2013401.","journal-title":"Virchows Arch"},{"key":"1917_CR22","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.7055","volume":"13","author":"C Chen","year":"2024","unstructured":"Chen C, Xu J, Zhang JX, Chen LY, Wei YA, Zhang WM, et al. CD2AP is a potential prognostic biomarker of renal clear cell carcinoma. Cancer Med. 2024;13:e7055.","journal-title":"Cancer Med"},{"key":"1917_CR23","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1002\/hep.30073","volume":"68","author":"H Zhang","year":"2018","unstructured":"Zhang H, Zhang C, Tang H, Gao S, Sun F, Yang Y, et al. CD2-associated protein contributes to hepatitis C, virus propagation and steatosis by disrupting insulin signaling. Hepatology. 2018;68:1710\u201325.","journal-title":"Hepatology"},{"key":"1917_CR24","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1002\/mc.23158","volume":"59","author":"W Xie","year":"2020","unstructured":"Xie W, Chen C, Han Z, Huang J, Liu X, Chen H, et al. CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly. Mol Carcinog. 2020;59:339\u201352.","journal-title":"Mol Carcinog"},{"key":"1917_CR25","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1126\/science.286.5438.312","volume":"286","author":"NY Shih","year":"1999","unstructured":"Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O, et al. Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science. 1999;286:312\u20135.","journal-title":"Science"},{"key":"1917_CR26","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1385\/IR:32:1-3:247","volume":"32","author":"AS Shaw","year":"2005","unstructured":"Shaw AS. T-cell activation and immunologic synapse. Immunol Res. 2005;32:247\u201352.","journal-title":"Immunol Res"},{"key":"1917_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007053","volume":"14","author":"S Raju","year":"2018","unstructured":"Raju S, Kometani K, Kurosaki T, Shaw AS, Egawa T. The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection. PLoS Pathog. 2018;14:e1007053.","journal-title":"PLoS Pathog"},{"key":"1917_CR28","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.molimm.2009.11.004","volume":"47","author":"Y Ma","year":"2010","unstructured":"Ma Y, Yang H, Qi J, Liu D, Xiong P, Xu Y, et al. CD2AP is indispensable to multistep cytotoxic process by NK cells. Mol Immunol. 2010;47:1074\u201382.","journal-title":"Mol Immunol"},{"key":"1917_CR29","doi-asserted-by":"publisher","first-page":"3778","DOI":"10.1182\/blood-2007-10-117531","volume":"111","author":"T Marafioti","year":"2008","unstructured":"Marafioti T, Paterson JC, Ballabio E, Reichard KK, Tedoldi S, Hollowood K, et al. Novel markers of normal and neoplastic human plasmacytoid dendritic cells. Blood. 2008;111:3778\u201392.","journal-title":"Blood"},{"key":"1917_CR30","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/S1470-2045(21)00151-0","volume":"22","author":"PR Galle","year":"2021","unstructured":"Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:991\u20131001.","journal-title":"Lancet Oncol"},{"key":"1917_CR31","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.annonc.2024.02.005","volume":"35","author":"B Sangro","year":"2024","unstructured":"Sangro B, Chan SL, Kelley RK, Lau G, Kudo M, Sukeepaisarnjaroen W, et al. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Ann Oncol. 2024;35:448\u201357.","journal-title":"Ann Oncol"},{"key":"1917_CR32","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/j.jhep.2023.03.003","volume":"79","author":"L Rimassa","year":"2023","unstructured":"Rimassa L, Finn RS, Sangro B. Combination immunotherapy for hepatocellular carcinoma. J Hepatol. 2023;79:506\u201315.","journal-title":"J Hepatol"}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-025-01917-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-025-01917-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-025-01917-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T02:30:04Z","timestamp":1763433004000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-025-01917-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,18]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1917"],"URL":"https:\/\/doi.org\/10.1007\/s10238-025-01917-3","relation":{},"ISSN":["1591-9528"],"issn-type":[{"value":"1591-9528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,18]]},"assertion":[{"value":"18 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2025","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 that there is no conflict of interest with regard to publication of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All sample tissues collection was approved by the Ethics Committees of Sun Yat-sen Memorial Hospital (Protocol number: SYSKY-2024\u2013095-01) in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all patients for the use and publication of their clinical data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"5"}}