Loss of OBSCN expression promotes bladder cancer progression but enhances the efficacy of PD-L1 inhibitors
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Abstract Background As the objective overall response rate to immune checkpoint inhibitors (ICIs) is less than 30% in late stage or metastatic bladder cancer (BLCA), elucidating the intrinsic mechanisms of immune evasion is of great importance for the discovery of predictive and prognostic biomarkers and the exploration of novel targets for intervention. Recent studies have shown that OBSCN and the cytoskeletal protein it encodes, obscurin, play an important role in tumour progression. However, no studies have reported the role of OBSCN in BLCA. Methods RNA sequencing and clinical data were downloaded from multiple public databases including The Cancer Genome Atlas and the Gene Expression Omnibus. Immunohistochemistry (IHC) was performed on tissue microarrays including 80 BLCA patients from Shuguang Hospital. Kaplan-Meier curves with log-rank test, univariate and multivariate COX regression were performed to evaluate the prognostic efficacy of OBSCN expression. In vitro experiments were conducted to determine the role of OBSCN deficiency in promoting BLCA progression. Pan-cancer tumour immune microenvironment (TIME) analysis was performed to explore the potential correlation between OBSCN deficiency and immune evasion. Results Pan-cancers and single-cell sequencing analysis revealed that the expression level and proportion of OBSCN was significantly decreased in BLCA cells compared to normal urothelium. Survival curves showed that BLCA patients with low OBSCN expression had a worse prognosis, yet a better clinical response to PD-L1 ICIs. Gene set variation analysis and Gene set enrichment analysis revealed that epithelial-mesenchymal transition (EMT) and immune-related processes were significantly enriched in BLCA samples with low OBSCN expression. In vitro experiments identified that OBSCN-deficient BLCA cells enhanced invasion, migration and EMT. Pan-cancer analysis of TIME revealed that neoantigen, tumor mutation burden, CD8+T cells and immune checkpoints were significantly negatively associated with OBSCN expression. IHC and Western blot assay identified that BLCA samples with low OBSCN expression had more CD8+ T-cell infiltration and higher PD-L1 expression. Conclusions This study confirmed that BLCA patients with low OBSCN expression had a worse prognosis but a superior response to ICIs, providing a reference for individualised treatment of BLCA patients.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Loss of OBSCN expression promotes bladder cancer progression but enhances the efficacy of PD-L1 inhibitors
- Date Crossref
- 27/03/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Shanghai University of Traditional Chinese Medicine Department of Urology pays non établi dans la noticeUniversité ou école supérieure
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Shuguang Hospital pays non établi dans la noticeÉtablissement de santé
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Shanghai Jiao Tong University Department of Urology pays non établi dans la noticeUniversité ou école supérieure
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Shanghai First People's Hospital pays non établi dans la noticeÉtablissement de santé
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Ruijin Hospital pays non établi dans la noticeÉtablissement de santé
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YangPu Geriatric Hospital pays non établi dans la noticeÉtablissement de santé
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Renji Hospital pays non établi dans la noticeÉtablissement de santé
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Tongren Hospital pays non établi dans la noticeÉtablissement de santé
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Shanghai Geriatric Medical Center Department of Urology pays non établi dans la noticeÉtablissement de santé
Department of Urology — Shanghai University of Traditional Chinese Medicine, Shuguang Hospital et Department of Urology — Shanghai Jiao Tong University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.