{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T04:22:22Z","timestamp":1787458942558,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010822","name":"Chengdu Science and Technology Bureau","doi-asserted-by":"crossref","award":["2024-YF05-00208-SN"],"award-info":[{"award-number":["2024-YF05-00208-SN"]}],"id":[{"id":"10.13039\/501100010822","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2024-YF05-00208-SN"],"award-info":[{"award-number":["2024-YF05-00208-SN"]}],"id":[{"id":"https:\/\/ror.org\/00xfea068","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Objective: Patients with systemic lupus erythematosus (SLE) exhibit elevated malignancy risk, with increased bladder cancer incidence. This study integrated Mendelian randomization (MR) with single-cell sequencing (scRNA-seq) to nominate exploratory prioritized candidate genes in SLE\u2013bladder cancer comorbidity and their T cell regulatory roles. Methods: Single-cell datasets for SLE (GSE266852) and bladder cancer (GSE222315) were retrieved from GEO. Quality control, clustering, and annotation were performed using Seurat. T cell differentially expressed genes were intersected for bidirectional two-sample MR using IEU Open GWAS statistics. Heterogeneity, pleiotropy, and sensitivity analyses assessed robustness. GeneMANIA, miRNA databases, and CTD were used for network and functional analyses. Wilcoxon tests and Monocle 2 were used to characterize expression and T cell differentiation trajectories. Results: Cross-disease intersection nominated 1010 candidate genes. In an exploratory MR screen (uncorrected p &lt; 0.05), four candidate genes were nominated (GBP3, LMAN1, SLC40A1, MIS18BP1); none survived FDR correction in both directions. At the uncorrected threshold, LMAN1 showed a shared risk direction (OR &gt; 1) and MIS18BP1 a protective direction (OR &lt; 1). Both showed significant T cell differential expression (p &lt; 0.001) and elevated late differentiation expression. LMAN1 was involved in COPII vesicle transport; MIS18BP1 in CENP-A chromatin assembly. Twenty high-confidence miRNAs targeted each gene. CTD indicated liver injury associations and cisplatin\/cyclosporine interactions. Conclusions: LMAN1 and MIS18BP1 are proposed as hypothesis-generating exploratory candidate genes in SLE\u2013bladder cancer comorbidity, potentially involved in immune dysregulation through T cell terminal differentiation modulation. This study provides preliminary evidence suggestive of autoimmune\u2013malignancy comorbidity mechanisms.<\/jats:p>","DOI":"10.3390\/life16081381","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:14:01Z","timestamp":1787300041000},"page":"1381","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Mendelian Randomization and Single-Cell Transcriptomics Reveal T Cell Immune Mechanisms in Systemic Lupus Erythematosus\u2013Bladder Cancer Comorbidity"],"prefix":"10.3390","volume":"16","author":[{"given":"Desheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjin","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16039","DOI":"10.1038\/nrdp.2016.39","article-title":"Systemic lupus erythematosus","volume":"2","author":"Kaul","year":"2016","journal-title":"Nat. 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