# Pan-Cancer Landscape of Magnesium Homeostasis: Bulk Omics Research and Single-Cell Sequencing Validation

## TL;DR

This study explores how magnesium balance affects cancer across 33 types, finding links to tumor growth, immunity, and potential new therapies.

## Contribution

The study introduces a magnesium homeostasis score (MHS) as a novel biomarker for cancer prognosis and immune response.

## Key findings

- Magnesium homeostasis-related genes like ANK3 and CNNM2 are downregulated in most tumors, correlating with better prognosis.
- Lower magnesium homeostasis scores are associated with reduced tumor mutational burden and immune dysfunction in cancers.
- Single-cell sequencing shows elevated magnesium homeostasis in CD8+ T cells, indicating a role in immune modulation.

## Abstract

Introduction: Magnesium homeostasis is critical for cellular growth and metabolism, yet its pan-cancer implications remain poorly characterized. This study aims to comprehensively analyze magnesium homeostasis across 33 cancer types, exploring its role in tumorigenesis, immune regulation, and therapeutic potential. Key magnesium homeostasis-related genes (e.g., ANK3, CNNM2) were significantly downregulated in most tumors, correlating with improved prognosis. Magnesium homeostasis scores (MHS) were reduced in cancers and linked to lower tumor mutational burden (TMB), microsatellite instability (MSI), immune dysfunction, and checkpoint gene expression. Single-cell sequencing revealed elevated MHS in CD8 + T cells, suggesting immune modulation roles. Conclusion: These findings highlight magnesium homeostasis as a regulator of tumor progression and immunity, with MHS serving as a prognostic biomarker. Targeting magnesium pathways may offer novel therapeutic strategies, warranting further clinical validation to advance personalized cancer therapies.

The online version contains supplementary material available at 10.1186/s12575-025-00294-1.