Triple-negative breast cancer (TNBC) is an aggressive subtype of mammary
carcinoma characterized by low expression levels of
estrogen receptor (ER),
progesterone receptor (PR), and
human epidermal growth factor receptor 2 (HER2). Along with the rapid development of the single-cell
RNA-sequencing (
scRNA-seq) technology, the heterogeneity within the tumor microenvironment (TME) could be studied at a higher resolution level, facilitating an exploration of the mechanisms leading to poor prognosis during
tumor progression. In previous studies,
hypoxia was considered as an intrinsic characteristic of TME in solid
tumors, which would activate downstream signaling pathways associated with angiogenesis and
metastasis. Moreover,
hypoxia-related genes (HRGs) based risk score models demonstrated nice performance in predicting the prognosis of TNBC patients. However, it is essential to further investigate the heterogeneity within hypoxic TME, such as intercellular communications. In the present study, utilizing single-sample Gene Set Enrichment Analysis (ssGSEA) and cell-cell communication analysis on the
scRNA-seq data retrieved from Gene Expression Omnibus (GEO) database with accession number GSM4476488, we identified four
tumor subpopulations with diverse functions, particularly a
hypoxia-related one. Furthermore, results of cell-cell communication analysis revealed the dominant role of the hypoxic
tumor subpopulation in angiogenesis- and
metastasis-related signaling pathways as a signal sender. Consequently, regard the TNBC cohorts acquired from The
Cancer Genome Atlas (TCGA) and GEO as train set and test set respectively, we constructed a risk score model with reliable capacity for the prediction of overall survival (OS), where ARTN and
L1CAM were identified as risk factors promoting angiogenesis and
metastasis of
tumors. The expression of ARTN and
L1CAM were further analyzed through
tumor immune estimation resource (TIMER) platform. In conclusion, these two marker genes of the hypoxic
tumor subpopulation played vital roles in
tumor development, indicating poor prognosis in TNBC patients.