{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T16:55:17Z","timestamp":1773161717809,"version":"3.50.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","license":[{"start":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:00:00Z","timestamp":1714694400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,3]]},"abstract":"<jats:p>Bladder Urothelial Carcinoma (BLCA), a prevalent and lethal cancer, lacks understanding regarding the roles and prognostic value of cuproptosis-related lncRNAs (CRLs), a novel form of cell death induced by copper. We collected RNA-seq data, clinical information, and prognostic data for 414 BLCA samples and 19 matched controls from The Cancer Genome Atlas. Using multivariate and univariate Cox regression analyses, we identified CRLs to create a prognostic signature. Patients were then divided into low- and high-risk groups based on their risk scores. We analyzed overall survival using the Kaplan\u2013Meier method, evaluated stromal and immune scores, and explored functional differences between these risk groups with gene set enrichment analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also conducted to understand the links between CRLs and BLCA development. We developed a prognostic signature using 4 independent CRLs: RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1. This signature independently predicted the prognosis of BLCA patients. High-risk patients had worse outcomes, with gene set enrichment analysis revealing enrichment in tumor- and immune-related pathways in the high-risk group. Notably, high-risk patients exhibited enhanced responses to immunotherapy and conventional chemotherapy drugs like sunitinib, paclitaxel, and gemcitabine. The independent prognostic signature variables RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1 predicted the prognoses of BLCA patients and provided a basis for the study of the mechanism of CRLs in BLCA development and progression, and the guidance of clinical treatments for patients with BLCA.<\/jats:p>","DOI":"10.1097\/md.0000000000038005","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T18:05:05Z","timestamp":1714759505000},"page":"e38005","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Identification of cuproptosis-related long non-coding RNA and construction of a novel prognostic signature for bladder cancer: An observational study"],"prefix":"10.1097","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3446-3745","authenticated-orcid":false,"given":"Zegen","family":"Ye","sequence":"first","affiliation":[{"name":"Lishui Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, Zhejiang 323000, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Lishui Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, Zhejiang 323000, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simin","family":"Wu","sequence":"additional","affiliation":[{"name":"Lishui Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, Zhejiang 323000, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxin","family":"Jin","sequence":"additional","affiliation":[{"name":"Lishui Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, Zhejiang 323000, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huajian","family":"Lin","sequence":"additional","affiliation":[{"name":"Lishui Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, Zhejiang 323000, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"Lishui Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, Zhejiang 323000, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuxia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Lishui Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, Zhejiang 323000, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4135-058X","authenticated-orcid":false,"given":"Zhaofu","family":"Guo","sequence":"additional","affiliation":[{"name":"Lishui Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, Zhejiang 323000, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20250504","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries (vol 68, pg 394, 2018).","volume":"68","author":"Bray","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"R2-20250504","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1001\/jama.2020.17598","article-title":"Bladder cancer: a review.","volume":"324","author":"Lenis","year":"2020","journal-title":"JAMA"},{"key":"R3-20250504","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.hoc.2021.02.004","article-title":"Diagnosis and staging of bladder cancer.","volume":"35","author":"Ahmadi","year":"2021","journal-title":"Hematol Oncol Clin North Am"},{"key":"R4-20250504","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins.","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science (New York, N.Y.)"},{"key":"R5-20250504","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41568-021-00417-2","article-title":"Connecting copper and cancer: from transition metal signalling to metalloplasia.","volume":"22","author":"Ge","year":"2022","journal-title":"Nat Rev Cancer"},{"key":"R6-20250504","doi-asserted-by":"crossref","first-page":"741316","DOI":"10.3389\/fmolb.2021.741316","article-title":"Recent advances in repurposing disulfiram and disulfiram derivatives as copper-dependent anticancer agents.","volume":"8","author":"Kannappan","year":"2021","journal-title":"Front Mol Biosci"},{"key":"R7-20250504","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1039\/C6MT00202A","article-title":"Defining the human copper proteome and analysis of its expression variation in cancers.","volume":"9","author":"Blockhuys","year":"2017","journal-title":"Metallomics"},{"key":"R8-20250504","doi-asserted-by":"crossref","first-page":"699804","DOI":"10.3389\/fcell.2021.699804","article-title":"A new ferroptosis-related lncRNA signature predicts the prognosis of bladder cancer patients.","volume":"9","author":"Chen","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"R9-20250504","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s12885-022-09377-8","article-title":"Comprehensive analysis of tumor immune microenvironment and prognosis of m6A-related lncRNAs in gastric cancer.","volume":"22","author":"Wang","year":"2022","journal-title":"BMC Cancer"},{"key":"R10-20250504","doi-asserted-by":"crossref","first-page":"1031906","DOI":"10.1155\/2021\/1031906","article-title":"Development of a Ferroptosis-Related lncRNA signature to predict the prognosis and immune landscape of bladder cancer.","volume":"2021","author":"Zhou","year":"2021","journal-title":"Dis Markers"},{"key":"R11-20250504","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1089\/jir.2020.0137","article-title":"Long-chain noncoding RNA ADAMTS9-AS2 regulates proliferation, migration, and apoptosis in bladder cancer cells through regulating miR-182-5p.","volume":"41","author":"Guo","year":"2021","journal-title":"J Interferon Cytokine Res"},{"key":"R12-20250504","doi-asserted-by":"crossref","first-page":"9620","DOI":"10.7150\/thno.44176","article-title":"LncRNA-SLC16A1-AS1 induces metabolic reprogramming during Bladder Cancer progression as target and co-activator of E2F1.","volume":"10","author":"Logotheti","year":"2020","journal-title":"Theranostics"},{"key":"R13-20250504","doi-asserted-by":"crossref","first-page":"930041","DOI":"10.3389\/fphar.2022.930041","article-title":"Comprehensive analysis of cuproptosis-related genes in immune infiltration and prognosis in melanoma.","volume":"13","author":"Lv","year":"2022","journal-title":"Front Pharmacol"},{"key":"R14-20250504","doi-asserted-by":"crossref","first-page":"8489387","DOI":"10.1155\/2022\/8489387","article-title":"A newly established cuproptosis-associated long non-coding RNA signature for predicting prognosis and indicating immune microenvironment features in soft tissue sarcoma.","volume":"2022","author":"Han","year":"2022","journal-title":"J Oncol"},{"key":"R15-20250504","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat Commun"},{"key":"R16-20250504","doi-asserted-by":"crossref","first-page":"807418","DOI":"10.3389\/fmolb.2022.807418","article-title":"Classification of hepatocellular carcinoma based on N6-methylandenosine-related lncRNAs profiling.","volume":"9","author":"Yin","year":"2022","journal-title":"Front Mol Biosci"},{"key":"R17-20250504","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data.","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf"},{"key":"R18-20250504","first-page":"7488188","article-title":"m6A-Related lncRNA to develop prognostic signature and predict the immune landscape in bladder cancer.","volume":"2021","author":"Li","year":"2021","journal-title":"J Oncol"},{"key":"R19-20250504","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/s41419-021-04296-1","article-title":"LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer.","volume":"12","author":"Luo","year":"2021","journal-title":"Cell Death Dis"},{"key":"R20-20250504","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41568-020-00313-1","article-title":"Advances in bladder cancer biology and therapy.","volume":"21","author":"Tran","year":"2021","journal-title":"Nat Rev Cancer"},{"key":"R21-20250504","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.1021\/acs.jmedchem.0c01936","article-title":"Dithiocarbazate-Copper complexes for bioimaging and treatment of pancreatic cancer.","volume":"64","author":"Gou","year":"2021","journal-title":"J Med Chem"},{"key":"R22-20250504","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/s41392-022-01014-x","article-title":"Cuproptosis: lipoylated TCA cycle proteins-mediated novel cell death pathway.","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct Targeted Ther"},{"key":"R23-20250504","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.molcel.2020.05.014","article-title":"Cell death in the origin and treatment of cancer.","volume":"78","author":"Strasser","year":"2020","journal-title":"Mol Cell"},{"key":"R24-20250504","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3390\/genes13050851","article-title":"A novel cuproptosis-related prognostic gene signature and validation of differential expression in clear cell renal cell carcinoma.","volume":"13","author":"Bian","year":"2022","journal-title":"Genes"},{"key":"R25-20250504","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/s41423-022-00866-1","article-title":"Cuproptosis: a new form of programmed cell death.","volume":"19","author":"Wang","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"R26-20250504","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/odi.12957","article-title":"Serum copper and zinc levels and the risk of oral cancer: a new insight based on large-scale case\u2013control study.","volume":"25","author":"Chen","year":"2019","journal-title":"Oral Dis"},{"key":"R27-20250504","doi-asserted-by":"crossref","first-page":"118893","DOI":"10.1016\/j.bbamcr.2020.118893","article-title":"Copper metabolism as a unique vulnerability in cancer.","volume":"1868","author":"Shanbhag","year":"2021","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"R29-20250504","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41422-022-00653-7","article-title":"Cuproptosis: a copper-triggered modality of mitochondrial cell death.","volume":"32","author":"Tang","year":"2022","journal-title":"Cell Res"},{"key":"R30-20250504","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fonc.2018.00095","article-title":"CDKN2A copy number loss is an independent prognostic factor in HPV-negative head and neck squamous cell carcinoma.","volume":"8","author":"Chen","year":"2018","journal-title":"Front Oncol"},{"key":"R31-20250504","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/ahg.12355","article-title":"MTF1 binds to metal-responsive element e within the ATP7B promoter and is a strong candidate in regulating the ATP7B expression.","volume":"84","author":"Stalke","year":"2020","journal-title":"Ann Hum Genet"},{"key":"R32-20250504","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s13258-019-00868-w","article-title":"Integrated analysis of quantitative proteome and transcriptional profiles reveals abnormal gene expression and signal pathway in bladder cancer.","volume":"41","author":"Liao","year":"2019","journal-title":"Genes Genom"},{"key":"R33-20250504","doi-asserted-by":"crossref","first-page":"e6036","DOI":"10.7717\/peerj.6036","article-title":"Identification of key candidate genes and biological pathways in bladder cancer.","volume":"6","author":"Gao","year":"2018","journal-title":"PeerJ"},{"key":"R34-20250504","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.7150\/jca.66248","article-title":"Niban apoptosis regulator 1 promotes gemcitabine resistance by activating the focal adhesion kinase signaling pathway in bladder cancer.","volume":"13","author":"Tong","year":"2022","journal-title":"J Cancer"},{"key":"R35-20250504","doi-asserted-by":"crossref","first-page":"10082","DOI":"10.1038\/s41598-022-14097-x","article-title":"Comprehensive analysis of the PD-L1 and immune infiltrates of N6-methyladenosine related long non-coding RNAs in bladder cancer.","volume":"12","author":"Xue","year":"2022","journal-title":"Sci Rep"},{"key":"R36-20250504","doi-asserted-by":"crossref","first-page":"827457","DOI":"10.3389\/fimmu.2022.827457","article-title":"Negative effects of stromal neutrophils on T Cells reduce survival in resectable urothelial carcinoma of the bladder.","volume":"13","author":"Yang","year":"2022","journal-title":"Front Immunol"},{"key":"R37-20250504","first-page":"41","article-title":"Neutrophil-to-lymphocyte ratio as a predictor of overall survival and cancer advancement in patients undergoing radical cystectomy for bladder cancer.","volume":"75","author":"Sudo\u0142","year":"2022","journal-title":"Central Eur J Urol"},{"key":"R38-20250504","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.immunol.26.021607.090331","article-title":"PD-1 and its ligands in tolerance and immunity.","volume":"26","author":"Keir","year":"2008","journal-title":"Annu Rev Immunol"},{"key":"R39-20250504","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1002\/cncr.22588","article-title":"PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression.","volume":"109","author":"Inman","year":"2007","journal-title":"Cancer"}],"container-title":["Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/MD.0000000000038005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T01:04:38Z","timestamp":1746320678000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/MD.0000000000038005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,3]]},"references-count":38,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.1097\/md.0000000000038005","relation":{},"ISSN":["0025-7974","1536-5964"],"issn-type":[{"value":"0025-7974","type":"print"},{"value":"1536-5964","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,3]]}}}