{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:07:44Z","timestamp":1790140064746,"version":"4.0.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>\n                    Disulfidptosis is a regulated cell-death program that occurs in SLC7A11-high cells under glucose limitation, but its relationship with oxidative stress in clear cell renal cell carcinoma (ccRCC) remains unclear. We integrated 313 oxidative stress-related genes with 24 disulfidptosis-related genes in the original TCGA-KIRC analysis. Pearson screening (|r| \u2265 0.8 and nominal two-sided P &amp;lt; 0.05) identified 21 disulfidptosis-oxidative stress (DOS) genes, from which three reported DOS subtypes, 63 subtype-associated genes and a four-gene score comprising\n                    <jats:italic>ZNF366<\/jats:italic>\n                    ,\n                    <jats:italic>EMCN<\/jats:italic>\n                    ,\n                    <jats:italic>GRIK3<\/jats:italic>\n                    and\n                    <jats:italic>NPR3<\/jats:italic>\n                    were derived. In an updated GDC-derived TCGA-KIRC dataset, both k = 3 classifications showed method-dependent stability, with weaker stability for the available 58-of-63-gene solution. Outcome-blind centroid transfer assigned all 101 E-MTAB-1980 cases and reproduced several molecular and immune\/stromal differences in GSE73731, although the hard clusters have not been independently validated for prognosis. In the atezolizumab-containing arms of IMmotion150, the within-cohort re-standardized four-gene score was lower in patients with clinical benefit and was associated with progression-free survival; the DOS21 module score was not associated with clinical benefit. The fixed four-gene score had modest internal discrimination (bootstrap optimism-corrected C-index, 0.697), and its transfer was sensitive to platform scaling and stage adjustment. Under the single 6-h glucose-deprivation condition,\n                    <jats:italic>NPR3<\/jats:italic>\n                    and\n                    <jats:italic>ZNF366<\/jats:italic>\n                    increased only in SLC7A11-high UMRC6 cells. Single-cell analyses in one VHL-related case and an independent 19-patient ccRCC cohort supported endothelial enrichment of\n                    <jats:italic>ZNF366<\/jats:italic>\n                    and showed that\n                    <jats:italic>NPR3<\/jats:italic>\n                    was not restricted to tumor cells. These findings identify\n                    <jats:italic>NPR3<\/jats:italic>\n                    and\n                    <jats:italic>ZNF366<\/jats:italic>\n                    as compartment-associated candidate markers but do not establish a functional role in disulfidptosis.\n                  <\/jats:p>","DOI":"10.3389\/fmolb.2026.1912537","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:50:10Z","timestamp":1790139010000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative oxidative stress\u2013disulfidptosis analysis identifies NPR3 and ZNF366 as cell-type-associated candidate markers in clear cell renal cell carcinoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Ping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Xi\u2019an International Medical Center Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixuan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Urology, Xi\u2019an International Medical Center Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaofeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, Xi\u2019an International Medical Center Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangfeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Urology, Xi\u2019an International Medical Center Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/nature08460","article-title":"Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1","volume":"462","author":"Barbie","year":"2009","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2013update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.ccell.2021.02.015","article-title":"Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma","volume":"39","author":"Bi","year":"2021","journal-title":"Cancer Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/s41591-020-0839-y","article-title":"Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma","volume":"26","author":"Braun","year":"2020","journal-title":"Nat. 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