Single-cell RNA sequencing and AlphaFold 3 insights into cytokine signaling and its role in uveal melanoma

Hongyan Sun ¹, Cunzi Li ¹, Zuhui Pu ^2,3

⁰Department of Ophthalmology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.

Frontiers in Immunology +

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February 7, 2025

View abstract on PubMed

Summary

This study reveals distinct cell subtypes and prognostic biomarkers in uveal melanoma (UVM), a challenging eye cancer. Findings offer new avenues for targeted therapies and personalized treatment strategies to improve patient survival.

Area Of Science

Oncology
Immunology
Genomics

Background

Uveal melanoma (UVM) is an aggressive eye cancer with poor prognosis, especially in metastatic stages.
Understanding cellular heterogeneity is crucial for identifying new therapeutic targets.

Purpose Of The Study

To elucidate the cellular heterogeneity within UVM.
To identify prognostic biomarkers for UVM.
To explore potential therapeutic targets within the UVM microenvironment.

Main Methods

Single-cell RNA sequencing (scRNA-seq) was performed on primary and metastatic UVM samples.
A UVM-specific gene signature was developed and validated.
Protein structures were predicted using AlphaFold 3; T-cell dynamics and immune responses were analyzed.

Main Results

ScRNA-seq identified five major cell types and seven distinct subtypes in UVM.
Differential expression of cytokine signaling in immune-related genes (CSIRGs) was observed across subtypes.
A validated UVM-specific gene signature correlated with overall survival; increased myeloid-derived suppressor cells (MDSCs) were noted in metastatic UVM.

Conclusions

The study identified key cellular subtypes and prognostic biomarkers in UVM.
Insights into cytokine signaling and T-cell dynamics provide a basis for personalized therapeutic strategies.
Findings pave the way for improved treatment approaches to enhance patient outcomes.

Keywords:

AlphaFold 3 Dictionary of Immune Responses to Cytokines T cell cytokine signaling single-cell RNA sequencing uveal melanoma