Downregulated granzyme M expression: implications for the immune system and prognosis of thyroid cancer

Jingying Pan1, Bidong Fu2, Shuhan Huang2

  • 1Department of Ultrasonography, Second Affiliated Hospital of Nanchang University, Nanchang, China; First College of Clinical Medicine, Nanchang University, China.

Gene
|April 14, 2025
PubMed

Insights

Granzyme family member GZMM is down-regulated in thyroid carcinoma (THCA), inhibiting tumor progression and linked to poor prognosis. Low GZMM expression may serve as a diagnostic and prognostic factor for THCA.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Thyroid carcinoma (THCA) is the most common endocrine cancer globally, with increasing incidence.
  • Granzyme family member GZMM plays a role in tumor cell inflammation and apoptosis.
  • The specific role of GZMM in THCA remains largely unexplored.

Purpose of the Study:

  • To investigate the expression, function, and prognostic significance of GZMM in thyroid carcinoma.
  • To explore the relationship between GZMM and the tumor immune microenvironment in THCA.
  • To develop a risk prediction model for THCA based on GZMM and epigenetic modifications.

Main Methods:

  • Bioinformatics analysis using TCGA and TIMER databases.
  • In vitro functional assays to assess GZMM's impact on angiogenesis, invasion, and migration.
  • Univariate and multivariate Cox regression and ROC curve analysis for prognostic evaluation.

Main Results:

  • GZMM protein levels are significantly down-regulated in THCA tissues and associated with clinicopathological features.
  • Low GZMM expression correlates with poor overall survival in THCA patients, indicating prognostic value.
  • GZMM inhibits tumor invasion, migration, and angiogenesis, and enhances CD8+ T cell infiltration.

Conclusions:

  • GZMM acts as a tumor suppressor in THCA by inhibiting invasion, migration, and angiogenesis.
  • GZMM expression is a significant prognostic biomarker for THCA and influences the tumor immune microenvironment.
  • A novel risk prediction model integrating GZMM and epigenetic modifications may aid in THCA management.

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