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<p>Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy associated with dismal prognosis. Migrasomes, a unique class of migration-dependent extracellular vesicles, have emerged as pivotal mediators of intercellular crosstalk within the tumor microenvironment. However, the clinical implications and regulatory mechanisms of migrasome-related long non-coding RNAs (MRLs) in HNSCC remain largely unexplored. Herein, we retrieved transcriptomic and clinical data of HNSCC from The Cancer Genome Atlas (TCGA) and established a prognostic signature using LASSO-Cox regression analysis, which was further internally validated in a randomly split subset of the TCGA cohort as internal validation. We systematically characterized the immune microenvironment and drug sensitivity profiles stratified by this signature, and identified the cellular distribution of core MRLs via single-cell RNA sequencing. Functional experiments were performed in clinical specimens and HNSCC cell lines using RT-qPCR, Western blot, CCK-8, and wound-healing assays. Consequently, a 10-MRL prognostic model was constructed to effectively stratify patients into high- and low-risk groups with significantly divergent overall survival, representing an independent prognostic factor in the context of the available clinical covariates from TCGA. High-risk patients exhibited an immunosuppressive tumor microenvironment and activation of oncogenic pathways (NF-κB, JAK-STAT). Mechanistically, MSC-AS1 was upregulated in HNSCC and facilitated cell proliferation and migration. Hypoxia upregulated the MSC-AS1/ITGA5 axis and increased VEGFA/PD-L1 expression, along with changes in the migrasome-related protein TSPAN4, suggesting a potential association with migrasome-related molecular features, which requires direct experimental validation. Collectively, our findings establish a novel MRL-based signature for prognostic prediction in HNSCC and highlight the hypoxia-responsive MSC-AS1/ITGA5 axis as a promising target for combinatorial therapeutic strategies.</p>

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A hypoxia-responsive migrasome-related lncRNA signature predicts prognosis and suggests the MSC-AS1/ITGA5 axis as a potential therapeutic target in head and neck squamous cell carcinoma

  • 期刊论文

  • 发表日期：

    2026年7月1日

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  • Sai Liang,
  • Xin Lin,
  • Fubo Wang,
  • Ming Yang,
  • Gang Qin

摘要

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy associated with dismal prognosis. Migrasomes, a unique class of migration-dependent extracellular vesicles, have emerged as pivotal mediators of intercellular crosstalk within the tumor microenvironment. However, the clinical implications and regulatory mechanisms of migrasome-related long non-coding RNAs (MRLs) in HNSCC remain largely unexplored. Herein, we retrieved transcriptomic and clinical data of HNSCC from The Cancer Genome Atlas (TCGA) and established a prognostic signature using LASSO-Cox regression analysis, which was further internally validated in a randomly split subset of the TCGA cohort as internal validation. We systematically characterized the immune microenvironment and drug sensitivity profiles stratified by this signature, and identified the cellular distribution of core MRLs via single-cell RNA sequencing. Functional experiments were performed in clinical specimens and HNSCC cell lines using RT-qPCR, Western blot, CCK-8, and wound-healing assays. Consequently, a 10-MRL prognostic model was constructed to effectively stratify patients into high- and low-risk groups with significantly divergent overall survival, representing an independent prognostic factor in the context of the available clinical covariates from TCGA. High-risk patients exhibited an immunosuppressive tumor microenvironment and activation of oncogenic pathways (NF-κB, JAK-STAT). Mechanistically, MSC-AS1 was upregulated in HNSCC and facilitated cell proliferation and migration. Hypoxia upregulated the MSC-AS1/ITGA5 axis and increased VEGFA/PD-L1 expression, along with changes in the migrasome-related protein TSPAN4, suggesting a potential association with migrasome-related molecular features, which requires direct experimental validation. Collectively, our findings establish a novel MRL-based signature for prognostic prediction in HNSCC and highlight the hypoxia-responsive MSC-AS1/ITGA5 axis as a promising target for combinatorial therapeutic strategies.