Exploring the Role of ERBB2 as a Potential Biomarker in Pan-Cancer: A Comprehensive Analysis

Abstract

ERBB2 is a gene encoding a receptor tyrosine kinase protein, which is responsible for regulating cell signal transduction, proliferation, and differentiation. Although ERBB2-targeted therapies have achieved remarkable success in breast cancer and gastric cancer, the molecular characteristics, functional consequences, and panorama of druggable mutations of ERBB2 across cancer types remain unclear. We integrated transcriptome data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases to define the ERBB2-high group based on the upper quartile of ERBB2 expression. The ERBB2-high group was significantly enriched in three core signaling pathways: RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, and JAK1/2-STAT3, with concurrent activation of the Notch and calcium signaling pathways. Differentially expressed gene (DEG) analysis was performed using DESeq2, and functional pathways were annotated via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Kaplan–Meier curves and multivariate Cox regression were used to evaluate the impact of ERBB2 expression on overall survival (OS), with additional comparisons to publicly available poziotinib clinical data. Furthermore, the distribution and panorama of ERBB2 mutations were mapped using the cBioPortal platform, and a heatmap predicting the pathogenicity of all ERBB2 missense mutations was constructed based on AlphaMissense data.