Triple-Negative Breast Cancer with High Levels of Annexin A1 Expression Is Associated with Mast Cell Infiltration, Inflammation, and Angiogenesis

Okano, Maiko; Oshi, Masanori; Butash, Ali; Katsuta, Eriko; Tachibana, Kazunoshin; Saito, Katsuharu; Okayama, Hirokazu; Peng, Xuan; Yan, Li; Kono, Koji; Ohtake, Toru; Takabe, Kazuaki

doi:10.3390/ijms20174197

Cited by 83 publications

(97 citation statements)

References 53 publications

(61 reference statements)

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“…Normalized microarray-based tumor gene expression and clinical data for 1903 patients of METABRIC cohort were obtained through the cBio portal, as we previously reported [48][49][50]. For the following studies, normalized microarray-based tumor gene expression and clinical data were obtained from Gene Expression Omnibus (GEO) repository (http://www.ncbi.nlm.ih.gov/geo/): Shi et al…”

Section: Data Of Metabric and Other Breast Cancer Cohortsmentioning

confidence: 99%

G2M Cell Cycle Pathway Score as a Prognostic Biomarker of Metastasis in Estrogen Receptor (ER)-Positive Breast Cancer

Oshi

Takahashi

Tokumaru

et al. 2020

IJMS

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105

107

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The vast majority of breast cancer death is a result of metastasis. Thus, accurate identification of patients who are likely to have metastasis is expected to improve survival. The G2M checkpoint plays a critical role in cell cycle. We hypothesized that breast cancer tumors with high activity of G2M pathway genes are more aggressive and likely to metastasize. To test this, we used the single-sample gene set variation analysis method to calculate the score for the Hallmark G2M checkpoint pathway using gene expression data of a total of 4626 samples from 12 human breast cancer cohorts. As expected, a high G2M pathway score correlated with enriched tumor expression of other cell proliferation-related gene sets. The score was significantly associated with clinical aggressive features of tumors and patient survival in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Interestingly, a high G2M score of metastasis tumors was also significantly associated with worse survival. In primary as well as metastasis tumors with high scores, the infiltration of both pro- and anti-cancerous immune cells increased. Tumor G2M score was also associated with treatment response to systemic chemotherapy in ER-positive/HER2-negative cancer, and was predictive of response to cyclin-dependent kinase inhibition therapy.

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Section: Data Of Metabric and Other Breast Cancer Cohortsmentioning

confidence: 99%

G2M Cell Cycle Pathway Score as a Prognostic Biomarker of Metastasis in Estrogen Receptor (ER)-Positive Breast Cancer

Oshi

Takahashi

Tokumaru

et al. 2020

IJMS

Self Cite

105

107

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“…Recent hypotheses suggest MCs have subsets with unique cytokine profiles similar to macrophage polarization and MCs are capable of switching between the subsets in a context-specific, localized manner, in other words, "tumor educated" MCs [57]. Aggressive triple-negative (ER − PR − HER2 − ) breast cancers were shown to have higher counts of infiltrating MCs and M2 macrophages mediated by higher expression of annexin A1 [58]. Such immune responses would benefit the progression of cancer through promoting chronic inflammation and wound repair pathways over cytotoxic pathways.…”

Section: Cancermentioning

confidence: 99%

Beyond IgE: Alternative Mast Cell Activation Across Different Disease States

Lyons

Pullen

2020

IJMS

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Mast cells are often regarded through the lens of IgE-dependent reactions as a cell specialized only for anti-parasitic and type I hypersensitive responses. However, recently many researchers have begun to appreciate the expansive repertoire of stimuli that mast cells can respond to. After the characterization of the interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis of mast cell activation—a pathway that is independent of the adaptive immune system—researchers are revisiting other stimuli to induce mast cell activation and/or subsequent degranulation independent of IgE. This discovery also underscores that mast cells act as important mediators in maintaining body wide homeostasis, especially through barrier defense, and can thus be the source of disease as well. Particularly in the gut, inflammatory bowel diseases (Crohn’s disease, ulcerative colitis, etc.) are characterized with enhanced mast cell activity in the context of autoimmune disease. Mast cells show phenotypic differences based on tissue residency, which could manifest as different receptor expression profiles, allowing for unique mast cell responses (both IgE and non-IgE mediated) across varying tissues as well. This variety in receptor expression suggests mast cells respond differently, such as in the gut where immunosuppressive IL-10 stimulates the development of food allergy or in the lungs where transforming growth factor-β1 (TGF-β1) can enhance mast cell IL-6 production. Such differences in receptor expression illustrate the truly diverse effector capabilities of mast cells, and careful consideration must be given toward the phenotype of mast cells observed in vitro. Given mast cells’ ubiquitous tissue presence and their capability to respond to a broad spectrum of non-IgE stimuli, it is expected that mast cells may also contribute to the progression of autoimmune disorders and other disease states such as metastatic cancer through promoting chronic inflammation in the local tissue microenvironment and ultimately polarizing toward a unique Th17 immune response. Furthermore, these interconnected, atypical activation pathways may crosstalk with IgE-mediated signaling differently across disorders such as parasitism, food allergies, and autoimmune disorders of the gut. In this review, we summarize recent research into familiar and novel pathways of mast cells activation and draw connections to clinical human disease.

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“…The scores of immune cells were downloaded from The Cancer Imaging Archive (TCIA) (https://tcia.at/home) database, and the correlation between the expression level of CBLL1 and tumor immune cells was analyzed. Screening criteria: P < 0.05 [20].…”

Section: Cibersortmentioning

confidence: 99%

The Role of M6A-related CBLL1 in the Prognosis and Immune Infiltration of Pan-cancer

Guo¹,

Li²,

Ji³

et al. 2020

Preprint

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Abstract Background The modification of N6-methyladenosine (m6A) plays an important role in physiology and disease progression. The relationship between the role of m6a-related gene CBLL1 in pan-carcinoma and tumor immune infiltrates has remained unknown. Methods To explore the expression level of CBLL1 methylation in pan-cancer in SMART database, and download mRNA expression, mutation and clinical data in UCSC database, to analyze the expression level of CBLL1, and the relationship between CBLL1 expression and clinicopathological features, prognosis, mutation and immune microenvironment in pan-cancer. CIBERSORT was used to analyze the relationship between the expression of CBLL1 and the infiltration of pan-carcinoma immune cells. The mRNA expression data of UCSC database were used to analyze the correlation between CBLL1 expression and pan-cancer immunomodulations, checkpoints and receptor molecules. Gene Set enrichment analysis (GSEA) revealed the possible mechanism of CBLL1 in the regulation of pan-cancer progression. Results The levels of CBLL1 methylation and mRNA expression in pan-cancer tissues were abnormal. The level of CBLL1 is related to the age, race, clinical stage and treatment effect of patients with pan-carcinoma and associated with the prognosis of patients with KIRC, LUSC, THCA, THYM, MESO, PRAD, STAD, and UVM. Univariate COX regression analysis showed that expression of CBLL1 was a risk factor for poor prognosis in patients with KICH, KIRC, LAML, THYM, KIRC, PCPG, OV, PRAD, STAD, GBM and UVM.The expression level of CBLL1 was correlated with BLCA, BRCA, COAD, LAML, LGG, LUAD, LUSC, SARC, STAD, THCA, THYM and UVM tumor mutational burden (TMB), and with ACC, BRCA, CESC, COAD, DLBC, HNSC, PRAD, READ, SARC, STAD, TGCT, THCA and UCEC microsatellite instability (MSI). The expression level of CBLL1 was correlated with pan-cancer stromal cells and immune cells. The expression of CBLL1 is related to pan-cancer immunomodulators, checkpoints and receptor molecules. GSEA found that CBLL1 may participate in the progression of pan-cancer through B cell receptor singaling pathway, mRNA binding, immunoglobulin receptor binding, Positive Regulation of cell cycle phase transition and other mechanisms. Conclusions CBLL1 is abnormally expressed in patients with pan-carcinoma, which is expected to be a biomarker for prognosis, mutation and immune infiltration in patients with pan-carcinoma.

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Triple-Negative Breast Cancer with High Levels of Annexin A1 Expression Is Associated with Mast Cell Infiltration, Inflammation, and Angiogenesis

Cited by 83 publications

References 53 publications

G2M Cell Cycle Pathway Score as a Prognostic Biomarker of Metastasis in Estrogen Receptor (ER)-Positive Breast Cancer

G2M Cell Cycle Pathway Score as a Prognostic Biomarker of Metastasis in Estrogen Receptor (ER)-Positive Breast Cancer

Beyond IgE: Alternative Mast Cell Activation Across Different Disease States

The Role of M6A-related CBLL1 in the Prognosis and Immune Infiltration of Pan-cancer

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