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Pan-cancer multi-omics profiling of MS4A2 unveils its functional landscape in lung adenocarcinoma

  • 0Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China.
International Journal of Surgery (london, England) +

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July 3, 2025

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July 3, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Membrane-spanning 4-domains subfamily A member 2 (MS4A2) acts as a prognostic marker in lung adenocarcinoma (LUAD), influencing survival and treatment sensitivity. High MS4A2 expression in LUAD indicates better outcomes and predicts response to specific therapies.

Area Of Science

  • Oncology
  • Immunology
  • Genomics

Background

  • The role of MS4A2 in cancer is complex and context-dependent.
  • Its prognostic significance across multiple survival metrics in lung adenocarcinoma (LUAD) is not well-defined.

Purpose Of The Study

  • To investigate the prognostic hierarchy of MS4A2 in LUAD across overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), and disease-free interval (DFI).
  • To explore the underlying biological mechanisms and potential therapeutic implications of MS4A2 in LUAD.

Main Methods

  • Integrated bulk and single-cell RNA sequencing data from TCGA/GTEx and NSCLC cohorts.
  • Applied Cox regression and Kaplan-Meier modeling for survival analyses.
  • Conducted immune infiltration, methylation, and drug sensitivity correlation analyses.

Main Results

  • MS4A2 expression was a significant LUAD-specific prognostic factor, with higher levels correlating with reduced mortality and prolonged disease control.
  • MS4A2, localized to tumor-associated mast cells, regulates leukocyte migration via bidirectional chemokine signaling.
  • Elevated MS4A2 expression was associated with female sex, earlier stage, and enhanced sensitivity to 5-fluorouracil and axitinib.

Conclusions

  • MS4A2 functions as a mast cell-driven regulator of LUAD progression, establishing an immunosuppressive niche paradoxically responsive to cytotoxic agents.
  • A precision stratification framework is proposed, suggesting MS4A2-high LUAD tumors benefit from 5-FU/axitinib combined with immunotherapy.
  • This study provides a quad-metric prognostic model linking mast cell biology to actionable LUAD management strategies.

Keywords: