An insight into the development of triple-negative breast cancer at transcriptome level based on single-cell sequencing technology

Abstract

Abstract Poor prognosis and low survival rate always hinder the research on the mechanism and pathology of triple-negative breast cancer (TNBC). With the rapid development of sequencing technology, the sequencing data of TNBC are becoming more widely available. This study attempted to reveal the potential biology of TNBC at both transcriptome and single-cell sequencing levels. Alteration in the differentially expression genes of TNBC was uncovered at the transcriptome level through the dataset GSE62931 and the cell ratio changes were displayed at the single-cell level through six samples from the dataset GSE161529. TNBC was identified at both transcriptome and single-cell levels. Compared with the non-TNBC group, 475 differentially expressed genes were obtained at the transcriptome level in the TNBC group. The differentially expressed genes were mainly enriched in microtubule binding, chromosome segregation, and response to xenobiotic stimulus, as well as pathways in cancer, Tyrosine metabolism, and Mucin type O-glycan biosynthesis. A sub-module with high correlation was further identified after screening of TNBC-related DEG. Compared with the non-TNBC group, the proportions of natural killer T cells, luminal epithelial cells, B cells, and basal cells in the TNBC group were significantly decreased at the single-cell level, but the proportions of T cells, monocytes, and neural progenitor cells significantly increased. The transcriptome results could be combined with the single-cell sequencing results through the submodule, based on which we studied the key genes related to the prognosis of TNBC patients, including RRM2, TPX2, CENPF and TOP2A. We found that the expression of these key genes at the single-cell level was heterogeneous with that at the overall cellular level. To conclude, the expression of RRM2, TPX2, CENPF, and TOP2A is heterogeneous at the cellular level, inconsistent with the expression of TNBC at the overall cellular level. Therefore, it is necessary to combine the changes at the gene level and the cellular level for research.