{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T01:08:56Z","timestamp":1783904936424,"version":"3.55.0"},"reference-count":55,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Background. Pancreatic adenocarcinoma (PAAD) is a malignancy with a very poor prognosis. The clinical significance of cuproptosis in PAAD combining single cell data with The Cancer Genome Atlas (TCGA) data is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      In this study, we first identified gene modules associated with cuproptosis by performing single-cell analysis and weighted co-expression network analysis (WCGNA). According to TCGA data, Cox regression and LASSO regression analysis were used to establish prognostic models, and PAAD patients were divided into high-risk and low-risk groups according to cuproptosis-related risk score. Then 7 algorithms were used to evaluate cancer immune microenvironment, followed by the mutation analysis. The expression levels and prognostic significance of the 8 model genes were analysed using single-gene analysis, Kaplan-Meier survival plots, and quantitative PCR (qPCR) validation. Finally, the biological function of\n                      <jats:italic>CEP55<\/jats:italic>\n                      in PAAD was verified by in vitro experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified cuproptosis-related genes (CRG) in PAAD by performing single-cell analysis and WCGNA, and constructed a cuproptosis-related prognostic model of PAAD by comprehensive bioinformatics analyses. Based on cuproptosis-related risk score, there were significant differences in survival time between two groups. We further constructed a cuproptosis-related risk score-based nomogram to accurately assess PAAD patient prognosis. Immune infiltration analysis revealed that PAAD samples with higher cuproptosis-related scores exhibited significantly lower immune infiltration levels, which may mechanistically underlie their poorer clinical outcomes. Furthermore, the high-risk group had a higher mutation rate of the same mutated gene, which means that they are more likely to benefit from immunotherapy. Finally, we identified that\n                      <jats:italic>CEP55<\/jats:italic>\n                      was significantly overexpressed in PAAD and correlated with poor patient prognosis. In vitro knockdown of\n                      <jats:italic>CEP55<\/jats:italic>\n                      effectively suppressed proliferation and invasion capabilities in pancreatic cancer cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this study, a novel prognostic model of PAAD was constructed to evaluate the prognosis and immune microenvironment of PAAD patients, and\n                      <jats:italic>CEP55<\/jats:italic>\n                      was identified as a central gene of PAAD. In vitro studies verified the biological function of\n                      <jats:italic>CEP55<\/jats:italic>\n                      , providing a new potential target for the treatment of PAAD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2478\/raon-2025-0042","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T07:59:51Z","timestamp":1752825591000},"page":"368-382","source":"Crossref","is-referenced-by-count":3,"title":["Cuproptosis-related gene\n                    <i>CEP55<\/i>\n                    as a biomarker of pancreatic adenocarcinoma via multi-omics techniques and experimental validation"],"prefix":"10.2478","volume":"59","author":[{"given":"Riyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, People\u2019s Hospital of Pingyang County , Wenzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixia","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Wenzhou Medical University , Wenzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurui","family":"Zhuang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Wenzhou Medical University , Wenzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhe","family":"Shi","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Wenzhou Medical University , Wenzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Guo","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology, Minhang Hospital, Fudan University , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, People\u2019s Hospital of Pingyang County , Wenzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"2026071215515274380_j_raon-2025-0042_ref_001","doi-asserted-by":"crossref","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. 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