Adipose-enriched peri-tumoral stroma, in contrast to myofibroblast-enriched stroma, prognosticates poorer survival in breast cancers
Despite our understanding of the genetic basis of intra-tumoral heterogeneity, the role of stromal heterogeneity arising from an altered tumor microenvironment in affecting tumorigenesis is poorly understood. In particular, extensive study on the peri-tumoral stroma in the morphologically normal tis...
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Main Authors: | , , , , , , , , , |
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Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2024
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Subjects: | |
Online Access: | https://hdl.handle.net/10356/173163 |
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Institution: | Nanyang Technological University |
Language: | English |
Summary: | Despite our understanding of the genetic basis of intra-tumoral heterogeneity, the role of stromal heterogeneity arising from an altered tumor microenvironment in affecting tumorigenesis is poorly understood. In particular, extensive study on the peri-tumoral stroma in the morphologically normal tissues surrounding the tumor is lacking. Here, we examine the heterogeneity in tumors and peri-tumoral stroma from 8 ER+/PR+/HER2- invasive breast carcinomas, through multi-region transcriptomic profiling by microarray. We describe the regional heterogeneity observed at the intrinsic molecular subtype, pathway enrichment, and cell type composition levels within each tumor and its peri-tumoral region, up to 7 cm from the tumor margins. Moreover, we identify a pro-inflammatory adipose-enriched peri-tumoral subtype which was significantly associated with poorer overall survival in breast cancer patients, in contrast to an adaptive immune cell- and myofibroblast-enriched subtype. These data together suggest that peri-tumoral heterogeneity may be an important determinant of the evolution and treatment of breast cancers. |
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