Identification of a migrasome-related lncRNA signature and its prognostic and immunological role in bladder cancer

Background: Bladder cancer (BLCA) is a highly heterogeneous malignancy with considerable variability in clinical outcomes. Reliable biomarkers for prognosis and treatment guidance remain urgently needed. Migrasomes, recently identified cellular organelles involved in intercellular communication, have been implicated in cancer progression, yet their associated long non-coding RNAs (lncRNAs) and prognostic relevance in BLCA remain unclear. Methods: We integrated transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) to identify migrasome-related lncRNAs through co-expression analysis. A prognostic signature was constructed using univariate Cox, LASSO, and multivariate regression analyses. Patients were stratified into high- and low-risk groups across training, validation, and entire cohorts. Kaplan-Meier survival, ROC curves, PCA, and Cox analyses were used for validation. Functional annotation was conducted via GO, KEGG, and GSEA. Immune infiltration and tumor microenvironment features were evaluated using ESTIMATE and CIBERSORT, while tumor mutation burden (TMB), immune escape potential, and drug sensitivity were also analyzed. Single-cell RNA sequencing (scRNA-seq) analysis delineated cellular heterogeneity and intercellular communication patterns related to the risk signature in the BLCA microenvironment. Finally, experimental validation of SEC24B-AS1, a key lncRNA within the model, was performed through qRT-PCR, CCK-8, colony formation, and migration assays to confirm its biological relevance. Results: A robust prognostic signature comprising migrasome-related lncRNAs was established, effectively distinguishing patients into high- and low-risk groups with significantly different survival outcomes. The signature remained an independent prognostic factor after multivariate adjustment. Functional enrichment analyses revealed marked biological distinctions between the two groups. Immune profiling showed higher immune and stromal scores in high-risk patients, together with distinct immune cell composition and function. High-risk tumors also exhibited elevated TMB and increased immune evasion potential. Drug sensitivity analysis identified compounds with differential responses between risk subgroups. Single-cell transcriptomic analysis indicated that the signature reflects cellular heterogeneity and intercellular communication patterns within the BLCA microenvironment. Experimental validation of SEC24B-AS1, a key lncRNA in the model, demonstrated its impact on tumor cell proliferation and migration, supporting the biological relevance of the prognostic signature in BLCA. Conclusion: This study presents a novel migrasome-related lncRNA signature that independently predicts survival in bladder cancer and reflects the tumor immune landscape.

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Journal
Frontiers in Immunology
Published
2026-04-16
DOI
https://doi.org/10.3389/fimmu.2026.1763443
Primary Topic
Cancer-related molecular mechanisms research
Type
article
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article

Identification of a migrasome-related lncRNA signature and its prognostic and immunological role in bladder cancer

Mingpeng Zhang, Junlin Shen, Heyang Guan, T Li et al.
Frontiers in Immunology
Cancer-related molecular mechanisms research
article

Identification of a migrasome-related lncRNA signature and its prognostic and immunological role in bladder cancer

Mingpeng Zhang, Junlin Shen, Heyang Guan, T Li, Yaqun Zhang, Zhiqun Shang, Liwei Liu, Chun Wang, Ruitao Li, Jing Tian
article en

Abstract

Background: Bladder cancer (BLCA) is a highly heterogeneous malignancy with considerable variability in clinical outcomes. Reliable biomarkers for prognosis and treatment guidance remain urgently needed. Migrasomes, recently identified cellular organelles involved in intercellular communication, have been implicated in cancer progression, yet their associated long non-coding RNAs (lncRNAs) and prognostic relevance in BLCA remain unclear. Methods: We integrated transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) to identify migrasome-related lncRNAs through co-expression analysis. A prognostic signature was constructed using univariate Cox, LASSO, and multivariate regression analyses. Patients were stratified into high- and low-risk groups across training, validation, and entire cohorts. Kaplan-Meier survival, ROC curves, PCA, and Cox analyses were used for validation. Functional annotation was conducted via GO, KEGG, and GSEA. Immune infiltration and tumor microenvironment features were evaluated using ESTIMATE and CIBERSORT, while tumor mutation burden (TMB), immune escape potential, and drug sensitivity were also analyzed. Single-cell RNA sequencing (scRNA-seq) analysis delineated cellular heterogeneity and intercellular communication patterns related to the risk signature in the BLCA microenvironment. Finally, experimental validation of SEC24B-AS1, a key lncRNA within the model, was performed through qRT-PCR, CCK-8, colony formation, and migration assays to confirm its biological relevance. Results: A robust prognostic signature comprising migrasome-related lncRNAs was established, effectively distinguishing patients into high- and low-risk groups with significantly different survival outcomes. The signature remained an independent prognostic factor after multivariate adjustment. Functional enrichment analyses revealed marked biological distinctions between the two groups. Immune profiling showed higher immune and stromal scores in high-risk patients, together with distinct immune cell composition and function. High-risk tumors also exhibited elevated TMB and increased immune evasion potential. Drug sensitivity analysis identified compounds with differential responses between risk subgroups. Single-cell transcriptomic analysis indicated that the signature reflects cellular heterogeneity and intercellular communication patterns within the BLCA microenvironment. Experimental validation of SEC24B-AS1, a key lncRNA in the model, demonstrated its impact on tumor cell proliferation and migration, supporting the biological relevance of the prognostic signature in BLCA. Conclusion: This study presents a novel migrasome-related lncRNA signature that independently predicts survival in bladder cancer and reflects the tumor immune landscape.

Frontiers in ImmunologyVol. 17
State Key Laboratory of Synthetic Chemistry (CN), Second Hospital of Tianjin Medical University (CN), Tongji Hospital (CN), Huazhong University of Science and Technology (CN), Tianjin Medical University (CN)
Openalex Percentile: Top 20%
Cancer-related molecular mechanisms research
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