Spatial transcriptomic analysis of a diverse patient cohort reveals a conserved architecture in triple-negative breast cancer.
Rania BassiouniMichael O IdowuLee D GibbsValentina RobilaPamela J GrizzardMichelle G WebbJiarong SongAshley NoriegaDavid W CraigJohn D CarptenPublished in: Cancer research (2022)
Triple-negative breast cancer (TNBC) is an aggressive disease that disproportionately affects African American (AA) women. Limited targeted therapeutic options exist for TNBC patients. Here, we employ spatial transcriptomics to interrogate tissue from a racially diverse TNBC cohort to comprehensively annotate the transcriptional states of spatially resolved cellular populations. A total of 38,706 spatial features from a cohort of 28 sections from 14 patients were analyzed. Intratumoral analysis of spatial features from individual sections revealed heterogeneous transcriptional substructures. However, integrated analysis of all samples resulted in nine transcriptionally distinct clusters that mapped across all individual sections. Furthermore, novel use of join count analysis demonstrated non-random directional spatial dependencies of the transcriptionally defined shared clusters, supporting a conserved spatio-transcriptional architecture in TNBC. These findings were substantiated in an independent validation cohort comprising 17,861 spatial features representing 15 samples from 8 patients. Stratification of samples by race revealed race-associated differences in hypoxic tumor content and regions of immune-rich infiltrate. Overall, this study combined spatial and functional molecular analyses to define the tumor architecture of TNBC, with potential implications in understanding TNBC disparities.
Keyphrases
- end stage renal disease
- ejection fraction
- newly diagnosed
- chronic kidney disease
- transcription factor
- african american
- peritoneal dialysis
- single cell
- prognostic factors
- type diabetes
- risk assessment
- metabolic syndrome
- cancer therapy
- skeletal muscle
- case report
- climate change
- oxidative stress
- polycystic ovary syndrome
- insulin resistance
- pregnancy outcomes