| Autor: |
Nanxin Zheng, Rongbo Wen, Leqi Zhou, Qingying Meng, Kuo Zheng, Zhixuan Li, Fuao Cao, Wei Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Translational Oncology, Vol 27, Iss , Pp 101570- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1936-5233 |
| DOI: |
10.1016/j.tranon.2022.101570 |
| Popis: |
Background: : The tumor microenvironment (TME) plays a critical role in shaping tumor progression and determining the outcome of the therapeutic response. In this study, we aimed to generate a comprehensive cellular landscape of the colorectal cancer (CRC) TME. Methods: : We generated a comprehensive single-cell atlas by collecting CRC cases that have been uploaded to the online database and conducting an in-depth secondary analysis. We then carried out spatial transcriptomic sequencing and multiple immunohistochemical analyses to verify the results of the single-cell analysis. Moreover, we applied our findings to the TCGA database and used tissue microarray (TMA) on CRC tissue specimens to validate clinical prognosis. Findings: We re-analyzed the transcriptomes of 23785 cells, revealing a pattern of cell heterogeneity in the tumor region, leading-edge region, and non-tumor region. A subtype of COL11A1+INHBA+ tumor-resident cancer-associated fibroblasts (CAFs) was identified, and marker genes, transcription factors, and tissue-specific expression differences were noted and suggested to have potential roles in promoting cancer. We further confirmed that COL11A1+INHBA+ tumor-resident CAFs are mainly located in the hypoxic TME and we propose that they interact with CD44+ CRC cells via INHBA. Elevation of INHBA in CRC is associated with a poor prognosis. Interpretation: : Our results demonstrated a single cell landscape of CRC in different regions and identified in hypoxic TME a special subtype of CAFs producing INHBA, which promotes CRC development and correlates with poor prognosis. This special subtype of CAFs is a candidate target for translational research. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
