Comprehensive single-cell and bulk transcriptomic analyses to develop an NK cell-derived gene signature for prognostic assessment and precision medicine in breast cancer

Qianshan Hou ¹, Chunzhen Li ¹, Yuhui Chong ²

⁰National Key Laboratory of Immunity & Inflammation, Institute of Immunology, Naval Medical University, Shanghai, China.

Frontiers in Immunology +

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November 7, 2024

View abstract on PubMed

Summary

This study developed a novel risk score using natural killer (NK) cell-related genes to predict breast cancer (BRCA) outcomes and guide personalized therapy. The NK-related risk scoring (NKRS) system shows promise for improving BRCA precision medicine.

Area Of Science

Oncology
Immunology
Genomics

Background

Natural killer (NK) cells are vital for anti-cancer immunity in breast cancer (BRCA).
Predictive markers and therapeutic targets based on NK cell-related molecules in BRCA are underexplored.
This study aimed to develop a prognostic and therapeutic prediction model for BRCA using NK cell-related genes.

Purpose Of The Study

To identify NK cell-related genes (NKRGs) associated with breast cancer prognosis.
To construct a prognostic signature and risk scoring system for BRCA.
To evaluate the model's predictive capability for treatment response and tumor microenvironment.

Main Methods

Utilized TCGA and GEO databases for data analysis.
Integrated single-cell and bulk transcriptomic analyses, including WGCNA and LASSO regression.
Validated key NKRGs using machine learning, spatial transcriptomics (ST), and immunohistochemistry (IHC).

Main Results

Identified 7 prognostic NKRGs and developed an NK-related risk scoring (NKRS) system.
NKRS demonstrated prognostic reliability and predicted immunotherapy and chemotherapeutic responses.
KLRB1 and CCND2 were validated as key prognostic NKRGs, with expression confirmed in BRCA specimens.

Conclusions

Developed a novel NK-related gene signature for BRCA prognosis and treatment response evaluation.
The NKRS system offers potential for advancing precision medicine in BRCA.
This signature can aid in predicting patient outcomes and guiding personalized therapeutic strategies.

Keywords:

breast cancer immunotherapy natural killer (NK) cell prognostic signature scRNA-seq tumor microenvironment