Transcriptomic Signatures in TP53 Positive and Negative Tumor Samples in NSCLC

Area of Science:

• Oncology
• Genomics
• Immunology

Background:

• Non-small cell lung cancer (NSCLC) is a major cause of cancer mortality globally.
• TP53 gene mutations are common in NSCLC and influence cancer development.
• Understanding transcriptomic differences based on TP53 status is crucial for targeted therapies.

Purpose of the Study:

• To identify differentially expressed genes (DEGs) associated with TP53 mutation status in NSCLC.
• To develop a prognostic gene signature for predicting overall survival.
• To assess the signature's ability to predict immune response, particularly for immunotherapy.

Main Methods:

• Analysis of gene expression profiles from NSCLC tumor samples (GEO and TCGA databases).
• Differential gene expression analysis to identify DEGs between TP53-mutated and TP53-wildtype groups.
• LASSO regression to develop a 12-gene prognostic signature and validation using qPCR.

Main Results:

• Identified 535 DEGs, narrowing down to a 12-gene signature with prognostic value.
• The 12-gene signature effectively stratified NSCLC patients into low- and high-risk groups for overall survival.
• Significant differences in immune cell infiltration and pathway activity were observed between risk groups, correlating with the gene signature.

Conclusions:

• The 12-gene signature shows strong predictive capability for survival and immune response in NSCLC.
• Findings suggest potential clinical utility in precision oncology and guiding immunotherapy strategies.
• The study provides insights into TP53 mutation-driven alterations in the tumor immune microenvironment.