Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer
Angiogenesis is one of the hallmarks of cancer. We hypothesized that intra-tumoral angiogenesis correlates with inflammation and metastasis in breast cancer patients. To test this hypothesis, we generated an angiogenesis pathway score using gene set variation analysis and analyzed the tumor transcri...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6708 |
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| author | Masanori Oshi Stephanie Newman Yoshihisa Tokumaru Li Yan Ryusei Matsuyama Itaru Endo Masayuki Nagahashi Kazuaki Takabe |
| author_facet | Masanori Oshi Stephanie Newman Yoshihisa Tokumaru Li Yan Ryusei Matsuyama Itaru Endo Masayuki Nagahashi Kazuaki Takabe |
| author_sort | Masanori Oshi |
| collection | DOAJ |
| description | Angiogenesis is one of the hallmarks of cancer. We hypothesized that intra-tumoral angiogenesis correlates with inflammation and metastasis in breast cancer patients. To test this hypothesis, we generated an angiogenesis pathway score using gene set variation analysis and analyzed the tumor transcriptome of 3999 breast cancer patients from The Cancer Genome Atlas Breast Cancer (TCGA-BRCA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), GSE20194, GSE25066, GSE32646, and GSE2034 cohorts. We found that the score correlated with expression of various angiogenesis-, vascular stability-, and sphingosine-1-phosphate (S1P)-related genes. Surprisingly, the angiogenesis score was not associated with breast cancer subtype, Nottingham pathological grade, clinical stage, response to neoadjuvant chemotherapy, or patient survival. However, a high score was associated with a low fraction of both favorable and unfavorable immune cell infiltrations except for dendritic cell and M2 macrophage, and with Leukocyte Fraction, Tumor Infiltrating Lymphocyte Regional Fraction and Lymphocyte Infiltration Signature scores. High-score tumors had significant enrichment for unfavorable inflammation-related gene sets (interleukin (IL)6, and tumor necrosis factor (TNF)α- and TGFβ-signaling), as well as metastasis-related gene sets (epithelial mesenchymal transition, and Hedgehog-, Notch-, and WNT-signaling). High score was significantly associated with metastatic recurrence particularly to brain and bone. In conclusion, using the angiogenesis pathway score, we found that intra-tumoral angiogenesis is associated with immune reaction, inflammation and metastasis-related pathways, and metastatic recurrence in breast cancer. |
| first_indexed | 2024-03-10T16:22:08Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:22:08Z |
| publishDate | 2020-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fd1825761edb426ebf126ea724ea27f42023-11-20T13:36:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118670810.3390/ijms21186708Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast CancerMasanori Oshi0Stephanie Newman1Yoshihisa Tokumaru2Li Yan3Ryusei Matsuyama4Itaru Endo5Masayuki Nagahashi6Kazuaki Takabe7Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, NY 14263, USABreast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, NY 14263, USABreast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, NY 14263, USADepartment of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, NY 14263, USADepartment of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, JapanBreast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, NY 14263, USAAngiogenesis is one of the hallmarks of cancer. We hypothesized that intra-tumoral angiogenesis correlates with inflammation and metastasis in breast cancer patients. To test this hypothesis, we generated an angiogenesis pathway score using gene set variation analysis and analyzed the tumor transcriptome of 3999 breast cancer patients from The Cancer Genome Atlas Breast Cancer (TCGA-BRCA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), GSE20194, GSE25066, GSE32646, and GSE2034 cohorts. We found that the score correlated with expression of various angiogenesis-, vascular stability-, and sphingosine-1-phosphate (S1P)-related genes. Surprisingly, the angiogenesis score was not associated with breast cancer subtype, Nottingham pathological grade, clinical stage, response to neoadjuvant chemotherapy, or patient survival. However, a high score was associated with a low fraction of both favorable and unfavorable immune cell infiltrations except for dendritic cell and M2 macrophage, and with Leukocyte Fraction, Tumor Infiltrating Lymphocyte Regional Fraction and Lymphocyte Infiltration Signature scores. High-score tumors had significant enrichment for unfavorable inflammation-related gene sets (interleukin (IL)6, and tumor necrosis factor (TNF)α- and TGFβ-signaling), as well as metastasis-related gene sets (epithelial mesenchymal transition, and Hedgehog-, Notch-, and WNT-signaling). High score was significantly associated with metastatic recurrence particularly to brain and bone. In conclusion, using the angiogenesis pathway score, we found that intra-tumoral angiogenesis is associated with immune reaction, inflammation and metastasis-related pathways, and metastatic recurrence in breast cancer.https://www.mdpi.com/1422-0067/21/18/6708angiogenesisbreast cancerepithelial-mesenchymal transitiongene setmetastatic recurrencesphingosine-1-phosphate |
| spellingShingle | Masanori Oshi Stephanie Newman Yoshihisa Tokumaru Li Yan Ryusei Matsuyama Itaru Endo Masayuki Nagahashi Kazuaki Takabe Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer International Journal of Molecular Sciences angiogenesis breast cancer epithelial-mesenchymal transition gene set metastatic recurrence sphingosine-1-phosphate |
| title | Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer |
| title_full | Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer |
| title_fullStr | Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer |
| title_full_unstemmed | Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer |
| title_short | Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer |
| title_sort | intra tumoral angiogenesis is associated with inflammation immune reaction and metastatic recurrence in breast cancer |
| topic | angiogenesis breast cancer epithelial-mesenchymal transition gene set metastatic recurrence sphingosine-1-phosphate |
| url | https://www.mdpi.com/1422-0067/21/18/6708 |
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