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pmid:32933189

Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer.

Masanori Oshi · Stephanie Newman · Yoshihisa Tokumaru · Li Yan · Ryusei Matsuyama · Itaru Endo · Masayuki Nagahashi · Kazuaki Takabe

International journal of molecular sciences · 2020 doi:10.3390/ijms21186708

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title
Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer.
doi
10.3390/ijms21186708
pmid
32933189
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[0]
Masanori Oshi
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Stephanie Newman
[2]
Yoshihisa Tokumaru
[3]
Li Yan
[4]
Ryusei Matsuyama
[5]
Itaru Endo
[6]
Masayuki Nagahashi
[7]
Kazuaki Takabe
journal
International journal of molecular sciences
year
2020
abstract
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.
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Kaplan–Meier curves with log-rank tests were used for survival analyses.
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The Cancer Genome Atlas Breast Cancer cohort (TCGA-BRCA) RNA-sequencing data and clinical information of 1065 patients, who were female and had pathological diagnosis of breast cancer, were obtained from Pan-Cancer Clinical Data Resource [33] and through the cBio Cancer Genomic Portal [61].
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sections[11] "4.1. Genetic Profiling and Clinical Information of Breast Cancer Cohorts" paragraph 2
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The Cancer Genome Atlas Breast Cancer cohort (TCGA-BRCA) RNA-sequencing data and clinical information of 1065 patients, who were female and had pathological diagnosis of breast cancer, were obtained from Pan-Cancer Clinical Data Resource [33] and through the cBio Cancer Genomic Portal [61].
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sample_count
286
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null
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96
taxon
Homo sapiens
title
Breast cancer relapse free survival
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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[3] object · 15 fields
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data:geo:GSE25066
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The Cancer Genome Atlas Breast Cancer cohort (TCGA-BRCA) RNA-sequencing data and clinical information of 1065 patients, who were female and had pathological diagnosis of breast cancer, were obtained from Pan-Cancer Clinical Data Resource [33] and through the cBio Cancer Genomic Portal [61].
structure object · 15 fields
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GEO
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GEO accession URL
access_statement_verbatim
The Cancer Genome Atlas Breast Cancer cohort (TCGA-BRCA) RNA-sequencing data and clinical information of 1065 patients, who were female and had pathological diagnosis of breast cancer, were obtained from Pan-Cancer Clinical Data Resource [33] and through the cBio Cancer Genomic Portal [61].
access_statement_kind
repository_route_statement
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sample_count
508
group_sizes
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group_sizes_basis
null
platform
96
taxon
Homo sapiens
title
Genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[4] object · 15 fields
id
data:geo:GSE32646
role
raw
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application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32646
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The Cancer Genome Atlas Breast Cancer cohort (TCGA-BRCA) RNA-sequencing data and clinical information of 1065 patients, who were female and had pathological diagnosis of breast cancer, were obtained from Pan-Cancer Clinical Data Resource [33] and through the cBio Cancer Genomic Portal [61].
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The Cancer Genome Atlas Breast Cancer cohort (TCGA-BRCA) RNA-sequencing data and clinical information of 1065 patients, who were female and had pathological diagnosis of breast cancer, were obtained from Pan-Cancer Clinical Data Resource [33] and through the cBio Cancer Genomic Portal [61].
access_statement_kind
repository_route_statement
sample_accessions array · 115 items
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Homo sapiens
title
GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer
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2026-11-01T15:39:54Z
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32933189", "kind": "science-record", "revision": 8, "content_hash": "sha256:22889293970eaa517c445a9b52e268abe3970ca94953a8358926b493fe364e3e", "created_at": "2026-11-01T15:41:10Z", "updated_at": "2026-11-01T22:02:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Recurrence in Breast Cancer.", "doi": "10.3390/ijms21186708", "pmid": "32933189", "authors": ["Masanori Oshi", "Stephanie Newman", "Yoshihisa Tokumaru", "Li Yan", "Ryusei Matsuyama", "Itaru Endo", "Masayuki Nagahashi", "Kazuaki Takabe"], "journal": "International journal of molecular sciences", "year": 2020, "abstract": "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. 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