Investigating Germ Cell Transition Genes in Breast Cancer: Exploring the Genesis of Cancer Testis-Associated Markers

Transition is an essential mechanism that drives the development of distinct cellular phenotypes and tumorigenesis. The expression of various types of testis cancer antigens (TCAs) in breast carcinomas suggests a potential transition to male germ cell features within the tumor. This study explores the cellular populations in breast cancer that express genes associated with male germ cell development. We re-analyzed published datasets to identify the germline-associated genes in breast tumors. We then experimentally validated the expression of the identified genes in 28 breast tissue tumor samples using a quantitative RT-PCR. Based on available datasets, we also performed single-cell RNA sequencing (scRNA-seq) to analyze the tumor heterogeneity and cellular clustering. A total of 455 overexpressed genes were identified that were related to fetal primordial germ cells (PGCs), particularly those in the male gonad. Our examinations showed a significant overexpression of five genes (CCNB1, CCNB2, PTTG1, RACGAP1, and UBE2C) in the tumor samples. The scRNA-seq analysis revealed 14 distinct cell clusters, characterized by different gene expression signatures and cell cycle phases. The breast tumor stromal cells were suggested as the main source of the germline-associated genes. This study provides insights into the molecular mechanisms and pathways involved in germ cell transition in breast carcinoma.