Integrative analyses of scRNA-seq and scATAC-seq reveal CXCL14 as a key regulator of lymph node metastasis in breast cancer.
Hum Mol Genet
; 30(5): 370-380, 2021 04 27.
Article
em En
| MEDLINE
| ID: mdl-33564857
ABSTRACT
The potentially different genetics and epigenetics in the primary tumors and metastases affect the efficacy of treatment in breast cancer patients. Nevertheless, the cellular and molecular mechanisms of breast cancer lymph node metastasis still remain elusive. Here, we employed single-cell RNA sequencing to acquire the transcriptomic profiles of individual cells from primary tumors, negative lymph nodes (NLs) and positive lymph nodes (PLs). We also performed a single-cell assay for transposase-accessible chromatin (ATAC) sequencing (scATAC-seq) of the positive and NL samples to get the chromatin accessibility profile. We identified a novel cell subpopulation with an abnormally high expression level of CXCL14 in the PL of breast cancer patients. Cell trajectory analysis also revealed that CXCL14 was increased expressed in the late pseudo-time. Moreover, based on a tissue microarray of 55 patients and the Oncomine database, we validated that CXCL14 expression was significantly higher in breast cancer patients with lymph node metastasis. Furthermore, scATAC-seq identified several transcription factors that may be potential regulation factors for the lymph node metastasis of breast cancer. Thus, our findings will improve our current understanding of the mechanism for lymph node metastasis, and they are potentially valuable in providing novel prognosis markers for the lymphatic metastasis of breast cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Cromatina
/
Regulação Neoplásica da Expressão Gênica
/
Quimiocinas CXC
/
Metástase Linfática
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article