{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:47:56Z","timestamp":1793764076379,"version":"4.6.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"DOI":"10.1007\/s12672-026-04753-3","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T19:14:37Z","timestamp":1772651677000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of the disulfidptosis-related gene G6PD as a potential biomarker and therapeutic target in pancreatic ductal adenocarcinoma by integrative bioinformatics analysis and experimental validation"],"prefix":"10.1007","volume":"17","author":[{"given":"Shuangyan","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bihua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XianYu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglin","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghao","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"4753_CR1","doi-asserted-by":"publisher","first-page":"2523","DOI":"10.3748\/wjg.v28.i22.2523","volume":"28","author":"QY Jiang","year":"2022","unstructured":"Jiang QY, Chen ZX, Zhang S, Xue RY. Future therapies for pancreatic carcinoma: insights into cancer precision medicine. World J Gastroenterol. 2022;28:2523\u20136. https:\/\/doi.org\/10.3748\/wjg.v28.i22.2523.","journal-title":"World J Gastroenterol"},{"key":"4753_CR2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. Cancer J Clin. 2023;73:17\u201348. https:\/\/doi.org\/10.3322\/caac.21763.","journal-title":"Cancer J Clin"},{"key":"4753_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.946266","volume":"13","author":"L Shang","year":"2022","unstructured":"Shang L, et al. Case report: Two PD-L1 positive unresectable advanced pancreatic carcinoma patients with microsatellite stability achieved R0 resection after PD-1 antibody plus chemotherapy as a successful downstaging therapy: A report of two cases. Front Immunol. 2022;13:946266. https:\/\/doi.org\/10.3389\/fimmu.2022.946266.","journal-title":"Front Immunol"},{"key":"4753_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-023-10615-w","volume":"23","author":"Y Nie","year":"2023","unstructured":"Nie Y, Liu C, Liu Q, Zhu X. CXCL10 is a prognostic marker for pancreatic adenocarcinoma and tumor microenvironment remodeling. BMC Cancer. 2023;23:150. https:\/\/doi.org\/10.1186\/s12885-023-10615-w.","journal-title":"BMC Cancer"},{"key":"4753_CR5","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41556-023-01091-2","volume":"25","author":"X Liu","year":"2023","unstructured":"Liu X, et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nat Cell Biol. 2023;25:404\u201314. https:\/\/doi.org\/10.1038\/s41556-023-01091-2.","journal-title":"Nat Cell Biol"},{"key":"4753_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-023-02675-4","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. https:\/\/doi.org\/10.1186\/s13046-023-02675-4.","journal-title":"J Exp Clin Cancer Res"},{"key":"4753_CR7","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408789","author":"J Wang","year":"2024","unstructured":"Wang J, et al. Inhibition of endoplasmic reticulum stress cooperates with SLC7A11 to promote disulfidptosis and suppress tumor growth upon glucose limitation. Adv Sci. 2024. https:\/\/doi.org\/10.1002\/advs.202408789.","journal-title":"Adv Sci"},{"key":"4753_CR8","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-025-01994-6","volume":"16","author":"X Wen","year":"2025","unstructured":"Wen X, et al. Disulfidptosis, a novel regulated cell death to predict survival and therapeutic response in kidney renal clear cell carcinoma. Discov Oncol. 2025;16:589. https:\/\/doi.org\/10.1007\/s12672-025-01994-6.","journal-title":"Discov Oncol"},{"key":"4753_CR9","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.gendis.2020.11.010","volume":"8","author":"X Liu","year":"2021","unstructured":"Liu X, Zhang Y, Zhuang L, Olszewski K, Gan B. NADPH debt drives redox bankruptcy: SLC7A11\/xCT-mediated cystine uptake as a double-edged sword in cellular redox regulation. Genes Dis. 2021;8:731\u201345. https:\/\/doi.org\/10.1016\/j.gendis.2020.11.010.","journal-title":"Genes Dis"},{"key":"4753_CR10","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1016\/j.apsb.2024.12.019","volume":"15","author":"Y Bei","year":"2025","unstructured":"Bei Y, et al. CDK5-triggered G6PD phosphorylation at threonine 91 facilitating redox homeostasis reveals a vulnerability in breast cancer. Acta Pharm Sin B. 2025;15:1608\u201325. https:\/\/doi.org\/10.1016\/j.apsb.2024.12.019.","journal-title":"Acta Pharm Sin B"},{"key":"4753_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-78911-4","author":"L Chen","year":"2024","unstructured":"Chen L, et al. Integrated multiomics analysis identified comprehensive crosstalk between diverse programmed cell death patterns and novel molecular subtypes in Hepatocellular Carcinoma. Sci Rep. 2024. https:\/\/doi.org\/10.1038\/s41598-024-78911-4.","journal-title":"Sci Rep"},{"key":"4753_CR12","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204782","author":"C Qi","year":"2023","unstructured":"Qi C, Ma J, Sun J, Wu X, Ding J. The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-associated genes in lung adenocarcinoma. Aging. 2023. https:\/\/doi.org\/10.18632\/aging.204782.","journal-title":"Aging"},{"key":"4753_CR13","doi-asserted-by":"crossref","unstructured":"Wu Q et al. Disulfidoptosis as a novel mechanism of neuronal death: insights from Creutzfeldt-Jakob Disease. 2024;191.","DOI":"10.1016\/j.wneu.2024.08.070"},{"key":"4753_CR14","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.36","author":"W Shen","year":"2022","unstructured":"Shen W, et al. Sangerbox: a comprehensive, interaction-friendly clinical bioinformatics analysis platform. iMeta. 2022. https:\/\/doi.org\/10.1002\/imt2.36.","journal-title":"iMeta"},{"key":"4753_CR15","doi-asserted-by":"crossref","unstructured":"H\u00e4nzelmann S, Castelo R, Guinney J. GSVA gene set variation analysis for microarray and RNA-seq data.pdf. 2013.","DOI":"10.1186\/1471-2105-14-7"},{"key":"4753_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3612","author":"K Yoshihara","year":"2013","unstructured":"Yoshihara K, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013. https:\/\/doi.org\/10.1038\/ncomms3612.","journal-title":"Nat Commun"},{"key":"4753_CR17","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17101599","author":"F Glapinski","year":"2025","unstructured":"Glapinski F, et al. The role of the tumor microenvironment in Pancreatic Ductal Adenocarcinoma: recent advancements and emerging therapeutic strategies. Cancers (Basel). 2025. https:\/\/doi.org\/10.3390\/cancers17101599.","journal-title":"Cancers (Basel)"},{"key":"4753_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.683332","volume":"12","author":"K Liu","year":"2021","unstructured":"Liu K, et al. IL-35 regulates the function of immune cells in tumor microenvironment. Front Immunol. 2021;12:683332. https:\/\/doi.org\/10.3389\/fimmu.2021.683332.","journal-title":"Front Immunol"},{"key":"4753_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0720-5","author":"O Yalcin","year":"2015","unstructured":"Yalcin O, et al. From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria. Malar J. 2015. https:\/\/doi.org\/10.1186\/s12936-015-0720-5.","journal-title":"Malar J"},{"key":"4753_CR20","unstructured":"Oronsky B et al. RRx-001, a novel clinical-stage chemosensitizer, radiosensitizer, and immunosensitizer, inhibits glucose 6-phosphate dehydrogenase in human tumor cells. 2016."},{"key":"4753_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1456649","author":"H Qin","year":"2025","unstructured":"Qin H. Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC. Front Immunol. 2025. https:\/\/doi.org\/10.3389\/fimmu.2024.1456649.","journal-title":"Front Immunol"},{"key":"4753_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-024-05279-2","author":"X Wu","year":"2025","unstructured":"Wu X. Disulfidptosis-related immune patterns predict prognosis and characterize the tumor microenvironment in oral squamous cell carcinoma. BMC Oral Health. 2025. https:\/\/doi.org\/10.1186\/s12903-024-05279-2.","journal-title":"BMC Oral Health"},{"key":"4753_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-025-03295-w","author":"H-F Yao","year":"2025","unstructured":"Yao H-F. CASC8 activates the pentose phosphate pathway to inhibit disulfidptosis in pancreatic ductal adenocarcinoma though the c-Myc-GLUT1 axis. J Exp Clin Cancer Res. 2025. https:\/\/doi.org\/10.1186\/s13046-025-03295-w.","journal-title":"J Exp Clin Cancer Res"},{"key":"4753_CR24","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.3892\/or.2020.7803","volume":"44","author":"R Li","year":"2020","unstructured":"Li R, Wang W, Yang Y, Gu C. Exploring the role of glucose\u20136\u2013phosphate dehydrogenase in cancer (Review). Oncol Rep. 2020;44:2325\u201336. https:\/\/doi.org\/10.3892\/or.2020.7803.","journal-title":"Oncol Rep"},{"key":"4753_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242417238","author":"A Ahamed","year":"2023","unstructured":"Ahamed A, Hosea R, Wu S, Kasim V. The emerging roles of the metabolic regulator G6PD in human cancers. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms242417238.","journal-title":"Int J Mol Sci"},{"key":"4753_CR26","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.7150\/ijbs.94220","volume":"20","author":"F Lu","year":"2024","unstructured":"Lu F, et al. Thioredoxin 1 supports colorectal cancer cell survival and promotes migration and invasion under glucose deprivation through interaction with G6PD: erratum. Int J Biol Sci. 2024;20:1410\u20132. https:\/\/doi.org\/10.7150\/ijbs.94220.","journal-title":"Int J Biol Sci"},{"key":"4753_CR27","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1158\/0008-5472.Can-06-2030","volume":"67","author":"C Li","year":"2007","unstructured":"Li C, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030\u20137. https:\/\/doi.org\/10.1158\/0008-5472.Can-06-2030.","journal-title":"Cancer Res"},{"key":"4753_CR28","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/nature07733","volume":"458","author":"M Diehn","year":"2009","unstructured":"Diehn M, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009;458:780\u20133. https:\/\/doi.org\/10.1038\/nature07733.","journal-title":"Nature"},{"key":"4753_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2021.145903","author":"Y Zhang","year":"2021","unstructured":"Zhang Y. Identification of biomarkers for acute leukemia via machine learning-based stemness index. Gene. 2021. https:\/\/doi.org\/10.1016\/j.gene.2021.145903.","journal-title":"Gene"},{"key":"4753_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/genes11030257","author":"Y Zhang","year":"2020","unstructured":"Zhang Y. mRNAsi index: machine learning in mining lung adenocarcinoma stem cell biomarkers. Genes. 2020. https:\/\/doi.org\/10.3390\/genes11030257.","journal-title":"Genes"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-026-04753-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-04753-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-04753-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:25:34Z","timestamp":1775820334000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-026-04753-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4753"],"URL":"https:\/\/doi.org\/10.1007\/s12672-026-04753-3","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"assertion":[{"value":"5 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This retrospective study was conducted in accordance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of the First Affiliated Hospital of Dali University (approval No. DFY204927001).\u00a0Individual informed consent was waived by the same committee because the study used only archival paraffin-embedded tissues and posed no additional risk to patients. All patient data were de-identified before analysis.\u00a0The individual informed consent requirements for this retrospective study have been officially approved for exemption by the Medical Ethics Committee of the First Affiliated Hospital of Dali University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and\u00a0consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"556"}}