Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma
IntroductionClear cell renal cell carcinoma (ccRCC) is characterized by high recurrence and metastasis rates, leading to poor prognosis. Migrasomes, a class of organelles mediating intercellular communication, and long noncoding RNAs (lncRNAs) both play critical roles in tumor progression; however,...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1638792/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849233666723545088 |
|---|---|
| author | Junlin Shen Chun Wang Mingpeng Zhang Bin Chen Liwei Liu Jing Tian Zhiqun Shang |
| author_facet | Junlin Shen Chun Wang Mingpeng Zhang Bin Chen Liwei Liu Jing Tian Zhiqun Shang |
| author_sort | Junlin Shen |
| collection | DOAJ |
| description | IntroductionClear cell renal cell carcinoma (ccRCC) is characterized by high recurrence and metastasis rates, leading to poor prognosis. Migrasomes, a class of organelles mediating intercellular communication, and long noncoding RNAs (lncRNAs) both play critical roles in tumor progression; however, the prognostic significance of migrasome-associated lncRNAs in ccRCC remains unclear.MethodsMigrasome-associated lncRNAs were identified using The Cancer Genome Atlas (TCGA) dataset, and a prognostic risk signature was constructed. The associations between the model and overall survival (OS), functional enrichment, tumor mutation burden (TMB), tumor microenvironment (TME) characteristics, immune evasion, and drug sensitivity were evaluated. Single-cell transcriptomic analysis was performed to determine cell type–specific expression patterns and intercellular communication networks. Functional roles of key lncRNAs were validated in vitro using qRT-PCR, CCK-8 proliferation assays, wound-healing assays, Transwell assays, colony formation assays, immunofluorescence, and Western blotting.ResultsThe risk signature stratified patients into high- and low-risk groups with significantly different survival outcomes. High-risk patients exhibited elevated TMB and enhanced immune evasion potential. Drug sensitivity analysis revealed distinct therapeutic response profiles between the groups. Single-cell transcriptomic analysis uncovered pronounced cellular heterogeneity and TME characteristics associated with the prognostic signature. High-risk cells were predominantly enriched within tumor epithelial clusters and displayed distinct intercellular communication patterns. Knockdown of FOXD2-AS1 markedly suppressed tumor cell proliferation and migration and reduced the expression of migrasome marker proteins.DiscussionThis study presents a novel migrasome-associated lncRNA risk signature with significant prognostic and therapeutic implications for ccRCC. The signature captures distinct immune, genomic, and pharmacologic features, and its core lncRNAs may promote tumor progression through migrasome-mediated signaling pathways, warranting further mechanistic investigation. |
| format | Article |
| id | doaj-art-409b919de09849bbb41a7b231603c6ce |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-409b919de09849bbb41a7b231603c6ce2025-08-20T04:14:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16387921638792Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinomaJunlin ShenChun WangMingpeng ZhangBin ChenLiwei LiuJing TianZhiqun ShangIntroductionClear cell renal cell carcinoma (ccRCC) is characterized by high recurrence and metastasis rates, leading to poor prognosis. Migrasomes, a class of organelles mediating intercellular communication, and long noncoding RNAs (lncRNAs) both play critical roles in tumor progression; however, the prognostic significance of migrasome-associated lncRNAs in ccRCC remains unclear.MethodsMigrasome-associated lncRNAs were identified using The Cancer Genome Atlas (TCGA) dataset, and a prognostic risk signature was constructed. The associations between the model and overall survival (OS), functional enrichment, tumor mutation burden (TMB), tumor microenvironment (TME) characteristics, immune evasion, and drug sensitivity were evaluated. Single-cell transcriptomic analysis was performed to determine cell type–specific expression patterns and intercellular communication networks. Functional roles of key lncRNAs were validated in vitro using qRT-PCR, CCK-8 proliferation assays, wound-healing assays, Transwell assays, colony formation assays, immunofluorescence, and Western blotting.ResultsThe risk signature stratified patients into high- and low-risk groups with significantly different survival outcomes. High-risk patients exhibited elevated TMB and enhanced immune evasion potential. Drug sensitivity analysis revealed distinct therapeutic response profiles between the groups. Single-cell transcriptomic analysis uncovered pronounced cellular heterogeneity and TME characteristics associated with the prognostic signature. High-risk cells were predominantly enriched within tumor epithelial clusters and displayed distinct intercellular communication patterns. Knockdown of FOXD2-AS1 markedly suppressed tumor cell proliferation and migration and reduced the expression of migrasome marker proteins.DiscussionThis study presents a novel migrasome-associated lncRNA risk signature with significant prognostic and therapeutic implications for ccRCC. The signature captures distinct immune, genomic, and pharmacologic features, and its core lncRNAs may promote tumor progression through migrasome-mediated signaling pathways, warranting further mechanistic investigation.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1638792/fullclear cell renal cell carcinomamigrasomeprognostic signaturetumor mutation burdentumor immune microenvironmentdrug sensitivity |
| spellingShingle | Junlin Shen Chun Wang Mingpeng Zhang Bin Chen Liwei Liu Jing Tian Zhiqun Shang Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma Frontiers in Immunology clear cell renal cell carcinoma migrasome prognostic signature tumor mutation burden tumor immune microenvironment drug sensitivity |
| title | Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma |
| title_full | Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma |
| title_fullStr | Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma |
| title_full_unstemmed | Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma |
| title_short | Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma |
| title_sort | integrative bulk and single cell transcriptomic analysis identifies a migrasome associated lncrna signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma |
| topic | clear cell renal cell carcinoma migrasome prognostic signature tumor mutation burden tumor immune microenvironment drug sensitivity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1638792/full |
| work_keys_str_mv | AT junlinshen integrativebulkandsinglecelltranscriptomicanalysisidentifiesamigrasomeassociatedlncrnasignaturepredictiveofprognosisandimmunelandscapeinclearcellrenalcellcarcinoma AT chunwang integrativebulkandsinglecelltranscriptomicanalysisidentifiesamigrasomeassociatedlncrnasignaturepredictiveofprognosisandimmunelandscapeinclearcellrenalcellcarcinoma AT mingpengzhang integrativebulkandsinglecelltranscriptomicanalysisidentifiesamigrasomeassociatedlncrnasignaturepredictiveofprognosisandimmunelandscapeinclearcellrenalcellcarcinoma AT binchen integrativebulkandsinglecelltranscriptomicanalysisidentifiesamigrasomeassociatedlncrnasignaturepredictiveofprognosisandimmunelandscapeinclearcellrenalcellcarcinoma AT liweiliu integrativebulkandsinglecelltranscriptomicanalysisidentifiesamigrasomeassociatedlncrnasignaturepredictiveofprognosisandimmunelandscapeinclearcellrenalcellcarcinoma AT jingtian integrativebulkandsinglecelltranscriptomicanalysisidentifiesamigrasomeassociatedlncrnasignaturepredictiveofprognosisandimmunelandscapeinclearcellrenalcellcarcinoma AT zhiqunshang integrativebulkandsinglecelltranscriptomicanalysisidentifiesamigrasomeassociatedlncrnasignaturepredictiveofprognosisandimmunelandscapeinclearcellrenalcellcarcinoma |