{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:04:08Z","timestamp":1790697848563,"version":"4.1.0"},"reference-count":50,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"unspecified","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Scientific Research Innovation and Exploration Program","award":["JZXKCTS-2024-04"],"award-info":[{"award-number":["JZXKCTS-2024-04"]}]},{"name":"Jiading District Health Commission, Shanghai","award":["2023-KY-11"],"award-info":[{"award-number":["2023-KY-11"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2026,8,7]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Lupus nephritis (LN) exhibits substantial clinical and pathological heterogeneity. We aimed to define proteomics-based molecular subtypes of LN and identify candidate biomarkers for subtype discrimination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed formalin-fixed paraffin-embedded (FFPE) renal biopsy specimens from 292 patients with biopsy-proven LN from four tertiary hospitals using data-independent acquisition (DIA)-liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS) proteomics. Molecular subtypes were identified by non-negative matrix factorisation. Differential proteins, functional enrichment, immune pathway activity, protein\u2013protein interaction networks and subtype-associated clinical\/pathological features were evaluated. Extreme Gradient Boosting (XGBoost) with SHapley Additive exPlanations (SHAP) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression were used to identify key subtype-related features and derive a protein panel distinguishing proliferative (class III\/IV) from membranous (class V) LN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two stable molecular subtypes were identified, with 1002 differential proteins between them. Subtype_2 was enriched for interferon-related innate immunity, complement activation, phagocytosis-endocytosis-lysosome pathways and ribosome biogenesis\/RNA metabolism, whereas Subtype_1 was characterised by keratinisation and epithelial structural remodelling. Subtype_2 was associated with higher serum creatinine, lower estimated glomerular filtration rate and higher chronicity index. APOL1 showed discriminatory value between subtypes, and serum ELISA demonstrated a consistent pattern with FFPE proteomic findings. A five-protein LASSO panel achieved an area under the curve of approximately 0.76 for distinguishing class III\/IV from class V LN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DIA-based proteomic profiling of FFPE renal biopsies identifies biologically and clinically relevant LN molecular subtypes and may support tissue-informed classification and risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2026-002123","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:30:13Z","timestamp":1787322613000},"page":"e002123","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["DIA proteomics of FFPE renal biopsies reveals two molecular subtypes of lupus nephritis and identifies APOL1 as candidate biomarker for stratification"],"prefix":"10.1136","volume":"13","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Deparment of Nephrology, Jiading Branch, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology; 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Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengying","family":"Qin","sequence":"additional","affiliation":[{"name":"Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5781-4732","authenticated-orcid":false,"given":"Liou","family":"Cao","sequence":"additional","affiliation":[{"name":"Deparment of Nephrology, Jiading Branch, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"2026092908103317000_13.2.e002123.1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41572-019-0141-9","article-title":"Lupus nephritis","volume":"6","author":"Anders","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2026092908103317000_13.2.e002123.2","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-020-02732-3"},{"key":"2026092908103317000_13.2.e002123.3","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.04710420"},{"key":"2026092908103317000_13.2.e002123.4","doi-asserted-by":"crossref","DOI":"10.1186\/s12014-018-9188-y","article-title":"Reproducible proteomics sample preparation for single FFPE tissue slices using acid-labile surfactant and direct trypsinization","volume":"15","author":"F\u00f6ll","year":"2018","journal-title":"Clin Proteomics"},{"key":"2026092908103317000_13.2.e002123.5","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2023.102381","article-title":"Protocol for deep proteomic profiling of formalin-fixed paraffin-embedded specimens using a spectral library-free approach","volume":"4","author":"Soni","year":"2023","journal-title":"STAR Protoc"},{"key":"2026092908103317000_13.2.e002123.6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.35248\/0974-276X.12.19.503","article-title":"Quantitative Proteomics Using Formalin-fixed, Paraffin-embedded Biopsy Tissues in Inflammatory Disease","volume":"12","author":"Amarnani","year":"2019","journal-title":"J Proteomics Bioinform"},{"key":"2026092908103317000_13.2.e002123.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature01510"},{"key":"2026092908103317000_13.2.e002123.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2020.10.014"},{"key":"2026092908103317000_13.2.e002123.9","doi-asserted-by":"crossref","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 Bioinformatics"},{"key":"2026092908103317000_13.2.e002123.10","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2026092908103317000_13.2.e002123.11","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"2026092908103317000_13.2.e002123.12","unstructured":"Nori H , Jenkins S , Koch P , et al . 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