MGST1 drives lymph node metastasis in papillary thyroid carcinoma via mitochondrial metabolic reprogramming and immune suppression

04 Jun 20264 min read0 viewsJournal Feed

GIST (Key Takeaways)

Background. While papillary thyroid carcinoma (PTC) generally exhibits a favorable prognosis, a subset of patients experiences poorer outcomes, with lymph node metastasis (LNM) significantly increasing the risk of recurrence and correlating with a worse prognosis. Mitochondrial metabolic reprogramming and immune evasion play pivotal roles in driving lymph node metastasis; however, the specific actionable targets within these processes remain largely unexplored.
Methods. We constructed a multi-omics discovery framework by integrating TCGA/GTEx transcriptomics, a large-scale independent clinical cohort, and single-cell RNA sequencing. Both mitochondrial metabolic signatures and immune evasion landscapes were investigated to characterize their roles in driving LNM.
A consensus machine learning framework was deployed to isolate core drivers, which were rigorously validated through genetic manipulation and pharmacological assays. Results. Unsupervised clustering identified a high-risk “Mito-high” subtype, characterized by distinct metabolic reprogramming and an immunosuppressive microenvironment, in which CD8+ T cell depletion coincided with Treg enrichment.
Machine learning prioritized MGST1 as the core predictor, consistently ranking as a top feature in both the integrated TCGA/GTEx dataset and our independent cohort. The MGST1-based model demonstrated robust predictive performance, achieving an AUC of 0.833 in external validation.

Clinical Editorial

Summary

Frontiers in Immunology published a clinical update in Infectious Disease on 04 Jun 2026.

The item focuses on MGST1 drives lymph node metastasis in papillary thyroid carcinoma via mitochondrial metabolic reprogramming and immune suppression.

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