Adipose-enriched peri-tumoral stroma, in contrast to myofibroblast-enriched stroma, prognosticates poorer survival in breast cancers

• Main Authors: Lau, Hannah Si Hui, Tan, Veronique Kiak Mien, Tan, Benita Kiat Tee, Sim, Yirong, Quist, Jelmar, Thike, Aye Aye, Tan, Puay Hoon, Pervaiz, Shazib, Grigoriadis, Anita, Sabapathy, Kanaga
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2024
• Subjects: Science::Medicine; Science::Biological sciences; Progesterone Receptor; Breast Cancer
• Online Access: https://hdl.handle.net/10356/173163
• Institution: Nanyang Technological University

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.