Identification of SLC2A1 as a predictive biomarker for survival and response to immunotherapy in lung squamous cell carcinoma

Bo Hao ¹, Huixing Dong ², Rui Xiong ¹

⁰Department of Thoracic Surgery, Renmin Hospital of Wuhan University, No.238 Jiefang Road, Wuchang District, Wuhan 430060, China.

Computers in Biology and Medicine +

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February 29, 2024

View abstract on PubMed

Summary

Solute carrier family 2 member 1 (SLC2A1), or glucose transporter-1 (GLUT1), is upregulated in lung squamous cell carcinoma, correlating with poor survival and immunotherapy response. Inhibiting GLUT1 may offer new treatment strategies for LUSC patients.

Area Of Science

Oncology
Molecular Biology
Immunology

Background

Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell lung cancer with limited advanced-stage treatment options.
Identifying genes linked to survival and immunotherapy efficacy is crucial for LUSC patient management.

Purpose Of The Study

To investigate the role of solute carrier family 2 member 1 (SLC2A1), encoding glucose transporter-1 (GLUT1), in LUSC progression and response to therapy.
To explore the association between SLC2A1 expression, tumor microenvironment, and patient outcomes.

Main Methods

Differential gene expression analysis using TCGA LUSC bulk and single-cell RNA-sequencing data.
Prognostic gene identification, protein expression validation, and survival analyses.
In vitro experiments to elucidate mechanisms of SLC2A1 in macrophage polarization and response to immunochemotherapy.

Main Results

SLC2A1 (GLUT1) was upregulated in LUSC tissues and identified as an independent prognostic factor.
High SLC2A1 expression correlated with enriched glycolysis, increased protein lactylation, and SPP1+ macrophage abundance.
GLUT1 inhibition affected HIF-1α-induced macrophage polarization; SLC2A1 expression inversely correlated with immune checkpoint molecules (PD-1, TIGIT, CTLA4, LAG3).

Conclusions

Elevated GLUT1 expression in LUSC is linked to worse survival and poor pathological response to immunotherapy.
GLUT1 promotes M2 macrophage polarization, impacting the tumor microenvironment and treatment efficacy.
Targeting GLUT1 could inform personalized immunotherapy strategies for LUSC patients.

Keywords:

GLUT1 Glycolysis Immunotherapy Lung squamous cell carcinoma SLC2A1