Identification of Tumor Budding-Associated Genes in Breast Cancer through Transcriptomic Profiling and Network Diffusion Analysis

Abstract

Breast cancer has the highest diagnosis rate among all cancers. Tumor budding (TB) is recognized as a recent prognostic marker. Identifying genes specific to high-TB samples is crucial for hindering tumor progression and metastasis. In this study, we utilized an RNA sequencing technique, called TempO-Seq, to profile transcriptomic data from breast cancer samples, aiming to identify biomarkers for high-TB cases. Through differential expression analysis and mutual information, we identified seven genes (NOL4, STAR, C8G, NEIL1, SLC46A3, FRMD6, and SCARF2) that are potential biomarkers in breast cancer. To gain more relevant proteins, further investigation based on a protein–protein interaction network and the network diffusion technique revealed enrichment in the Hippo signaling and Wnt signaling pathways, promoting tumor initiation, invasion, and metastasis in several cancer types. In conclusion, these novel genes, recognized as overexpressed in high-TB samples, along with their associated pathways, offer promising therapeutic targets, thus advancing treatment and diagnosis for breast cancer.