Rongrong Wu1,2, Shipra Gandhi3, Yoshihisa Tokumaru1,4, Mariko Asaoka2, Masanori Oshi1,5, Li Yan6, Takashi Ishikawa2, Kazuaki Takabe7,8,9,10,11,12. 1. Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, NY, 14263, USA. 2. Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, 160-8402, Japan. 3. Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA. 4. Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, 501-1193, Japan. 5. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan. 6. Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA. 7. Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, NY, 14263, USA. kazuaki.takabe@roswellpark.org. 8. Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, 160-8402, Japan. kazuaki.takabe@roswellpark.org. 9. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan. kazuaki.takabe@roswellpark.org. 10. Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY, 14263, USA. kazuaki.takabe@roswellpark.org. 11. Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. kazuaki.takabe@roswellpark.org. 12. Department of Breast Surgery, Fukushima Medical University, Fukushima, Japan. kazuaki.takabe@roswellpark.org.
Abstract
PURPOSE: Platelet-derived growth factor B (PDGFB) is known to play essential roles in angiogenesis and lymphangiogenesis during development, and tumor growth and vessel stabilization in experimental models. However, whether these findings could be translated to breast cancer patients remains unclear. We hypothesized that PDGFB gene expression is associated with angiogenesis, cell proliferation, and clinical outcomes in breast cancer patients. METHODS: A total of 7635 primary breast cancer patients with full transcriptome and clinical data available from 13 independent cohorts were analyzed using in silico approach. The median value was used to divide each cohort into high and low PDGFB expression groups. RESULTS: High PDGFB gene expression was associated with increased expression of angiogenesis-related genes, higher amount of vascular cell infiltrations, and with enrichment of angiogenesis gene set, lymphangiogenesis-related gene expressions, lymphangiogenesis-related cell infiltrations, and enrichmentof lymphangiogenesis gene set in GSE96058 and validated by TCGA cohorts; however, not with lymphatic metastasis. PDGFB expression was neither associated with cell proliferation as assessed by Ki67 expression nor with Nottingham histological grade, or response to neoadjuvant chemotherapy. We found that PDGFB was most extensively expressed by endothelial and perivascular-like cells in the tumor microenvironment, and minimally by cancer cells consistently in two single-cell sequence cohorts. High PDGFB expression enriched TGFβ, epithelial-mesenchymal transition, hypoxia, and cancer stem cell-associated pathways. However, no association with distant metastasis was observed. Disease-specific and disease-free survival were worse in the high PDGFB expression group consistently in TCGA and METABRIC cohorts. CONCLUSION: PDGFB is predominantly expressed in endothelial cells and is associated with angiogenesis and lymphangiogenesis, but not with cellular proliferation or metastasis in breast cancer.
PURPOSE: Platelet-derived growth factor B (PDGFB) is known to play essential roles in angiogenesis and lymphangiogenesis during development, and tumor growth and vessel stabilization in experimental models. However, whether these findings could be translated to breast cancer patients remains unclear. We hypothesized that PDGFB gene expression is associated with angiogenesis, cell proliferation, and clinical outcomes in breast cancer patients. METHODS: A total of 7635 primary breast cancer patients with full transcriptome and clinical data available from 13 independent cohorts were analyzed using in silico approach. The median value was used to divide each cohort into high and low PDGFB expression groups. RESULTS: High PDGFB gene expression was associated with increased expression of angiogenesis-related genes, higher amount of vascular cell infiltrations, and with enrichment of angiogenesis gene set, lymphangiogenesis-related gene expressions, lymphangiogenesis-related cell infiltrations, and enrichmentof lymphangiogenesis gene set in GSE96058 and validated by TCGA cohorts; however, not with lymphatic metastasis. PDGFB expression was neither associated with cell proliferation as assessed by Ki67 expression nor with Nottingham histological grade, or response to neoadjuvant chemotherapy. We found that PDGFB was most extensively expressed by endothelial and perivascular-like cells in the tumor microenvironment, and minimally by cancer cells consistently in two single-cell sequence cohorts. High PDGFB expression enriched TGFβ, epithelial-mesenchymal transition, hypoxia, and cancer stem cell-associated pathways. However, no association with distant metastasis was observed. Disease-specific and disease-free survival were worse in the high PDGFB expression group consistently in TCGA and METABRIC cohorts. CONCLUSION: PDGFB is predominantly expressed in endothelial cells and is associated with angiogenesis and lymphangiogenesis, but not with cellular proliferation or metastasis in breast cancer.
Authors: Henrik C Nyström; Per Lindblom; Anna Wickman; Irene Andersson; Jenny Norlin; Jenny Fäldt; Per Lindahl; Ole Skøtt; Mattias Bjarnegård; Sharyn M Fitzgerald; Kenneth Caidahl; Li-ming Gan; Christer Betsholtz; Göran Bergström Journal: Cardiovasc Res Date: 2006-05-25 Impact factor: 10.787
Authors: Nynke M S Van den Akker; Leah C J Winkel; Maya H Nisancioglu; Saskia Maas; Lambertus J Wisse; Annika Armulik; Robert E Poelmann; Heleen Lie-Venema; Christer Betsholtz; Adriana C Gittenberger-de Groot Journal: Dev Dyn Date: 2008-02 Impact factor: 3.780