Comprehensive Analysis of RUNX and TGF-β Mediated Regulation of Immune Cell Infiltration in Breast Cancer

Runt-related transcription factors (RUNXs) can serve as both transcription activators and repressors during biological development, including immune cell maturation. RUNX factors have both tumor-promoting and tumor-suppressive roles in carcinogenesis. Immune cell infiltration and the tumor immune microenvironment have been found to be key regulators in breast cancer progression, treatment response, and patient outcome. However, the relationship between the RUNX family and immune cell infiltration in breast cancer remains unclear. We performed a comprehensive analysis to reveal the role of RUNX factors in breast cancer. Analysis of patient data in the Oncomine database showed that the transcriptional levels of RUNX proteins in breast cancer were elevated. Kaplan–Meier plotter (KM plotter) analysis showed that breast cancer patients with higher expression of RUNX proteins had better survival outcomes. Through analysis of the UALCAN database, we found that the transcriptional levels of RUNX factors were significantly correlated with some breast cancer patient characteristics. cBio Cancer Genomics Portal (cBioPortal) analysis showed the proportions of different RUNX genomic alterations in various subclasses of breast cancer. We also performed gene ontology (GO) and pathway analyses for the significantly differentially expressed genes that were correlated with RUNX factors in breast cancer. TIMER database analysis showed that immune cell infiltration in breast cancer could be affected by the transcriptional level, mutation, and gene copy number of RUNX proteins. Using the Gene Set Cancer Analysis (GSCA) database, we analyzed the effects of RUNX gene methylation on the level of immune cell infiltration in breast cancer. We found that the methylation level changes of RUNX2 and RUNX3 had opposite effects on immune cell infiltration in breast cancer. We also analyzed the relationship between the methylation level of RUNX genes and the TGF-β signaling pathway using the TISIDB database. The results showed that the methylation levels of RUNX1 and RUNX3 were correlated with the expression of TGF-β1. In summary, our analysis found that the RUNX family members can influence the infiltration of various immune cells in breast cancer depending on their expression level, mutation, gene copy number, and methylation. The RUNX family is an important regulator of immune cell infiltration in breast cancer and may serve as a potential prognostic biomarker.

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Abstract 4908: Deep sequence analysis of the relationship between gene expression, CpG island methylation, and gene copy number in breast cancer cells

10.1158/1538-7445.am2011-4908 ◽

2011 ◽

Author(s):

Zhifu Sun ◽

Yan W Asmann ◽

Krishna R Kalari ◽

Brian Bot ◽

Jeanette E Eckel-Passow ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Copy Number ◽

Breast Cancer Cells ◽

Cpg Island ◽

Gene Copy Number ◽

Gene Copy ◽

Cpg Island Methylation ◽

The Relationship ◽

Deep Sequence Analysis

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DNA polymerase β deficiency is linked to aggressive breast cancer: A comprehensive analysis of gene copy number, mRNA and protein expression in multiple cohorts

Molecular Oncology ◽

10.1016/j.molonc.2014.01.001 ◽

2014 ◽

Vol 8 (3) ◽

pp. 520-532 ◽

Cited By ~ 22

Author(s):

Tarek M.A. Abdel-Fatah ◽

Roslin Russell ◽

Devika Agarwal ◽

Paul Moseley ◽

Michael Ayotunde Abayomi ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Dna Polymerase ◽

Copy Number ◽

Gene Copy Number ◽

Comprehensive Analysis ◽

Gene Copy ◽

Dna Polymerase Β ◽

Mrna And Protein Expression ◽

Aggressive Breast Cancer

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Abstract P4-09-01: FGFR1 protein expression is associated with prognosis in primary breast cancer: A comprehensive analysis of gene copy number, mRNA and protein expression

10.1158/1538-7445.sabcs15-p4-09-01 ◽

2016 ◽

Author(s):

M Tomiguchi ◽

Y Yamamoto ◽

M Yamamoto-Ibusuki ◽

R Yamaguchi ◽

Y Fujiki ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Primary Breast Cancer ◽

Copy Number ◽

Gene Copy Number ◽

Comprehensive Analysis ◽

Gene Copy ◽

Mrna And Protein Expression

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Insulin-like growth factor-1 receptor gene expression is associated with survival in breast cancer: a comprehensive analysis of gene copy number, mRNA and protein expression

Breast Cancer Research and Treatment ◽

10.1007/s10549-011-1605-0 ◽

2011 ◽

Vol 130 (1) ◽

pp. 307-317 ◽

Cited By ~ 25

Author(s):

Peifen Fu ◽

Mutsuko Ibusuki ◽

Yutaka Yamamoto ◽

Mitsuhiro Hayashi ◽

Keiichi Murakami ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Growth Factor ◽

Copy Number ◽

Receptor Gene ◽

Gene Copy Number ◽

Comprehensive Analysis ◽

Gene Copy ◽

Mrna And Protein Expression ◽

Receptor Gene Expression

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Comprehensive Analysis of Pyroptosis-Related Genes and Tumor Microenvironment Infiltration Characterization in Breast Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2021.748221 ◽

2021 ◽

Vol 12 ◽

Author(s):

JianBin Wu ◽

Yuanyuan Zhu ◽

MingMin Luo ◽

Lei Li

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

Tumor Progression ◽

Immune Checkpoint ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Clinical Prognosis ◽

The Relationship ◽

Single Tumor

BackgroundImmunotherapy has emerged as a significant strategy to treat numerous tumors. The positive response to immunotherapy depends on the dynamic interaction between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Pyroptosis, inflammation-induced cell death, is intricately associated with several tumors. However, the relationship between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy effect is unclear in breast cancer (BRCA).MethodsWe comprehensively evaluated 33 pyroptosis-related genes and systematically assessed the relationship between pyroptosis and tumor progression, prognosis, and immune cell infiltration. The PyroptosisScore was used to quantify the pyroptosis pattern of a single tumor patient. We then assessed their values for predicting prognoses and therapeutic responses in BRCA.ResultsThree different modes of PyroptosisClusters were determined. The characteristics of TME cell infiltration in these three PyroptosisClusters were highly consistent with three immunophenotypes of tumors, including immune-excluded, immune-inflamed, and immune-desert phenotypes. Comprehensive bioinformatics analysis revealed that patients with a low PyroptosisScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, and were more sensitive to immunotherapy than those with a high PyroptosisScore.ConclusionsOur findings revealed the crucial role of pyroptosis in maintaining the diversity and complexity of TME. Pyroptosis is closely related to tumor progression, tumor prognosis, and immunotherapy response. Evaluating the PyroptosisScore of a single tumor can assist in understanding the characteristics of TME infiltration and lead to the development of more effective immunotherapy strategies.

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Faculty Opinions recommendation of Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725485692.793517744 ◽

2016 ◽

Author(s):

Paul Timpson ◽

Claire Vennin

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Immune Cell ◽

Cancer Invasion ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Human Breast ◽

Breast Cancer Invasion

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Nongenotoxic ABCB1 activator tetraphenylphosphonium can contribute to doxorubicin resistance in MX-1 breast cancer cell line

Scientific Reports ◽

10.1038/s41598-021-86120-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Raimonda Kubiliute ◽

Indre Januskeviciene ◽

Ruta Urbanaviciute ◽

Kristina Daniunaite ◽

Monika Drobniene ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Protein Level ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Common Mechanism ◽

Dna Hypomethylation ◽

Mesenchymal Transition ◽

Molecular Features

AbstractHyperactivation of ABC transporter ABCB1 and induction of epithelial–mesenchymal transition (EMT) are the most common mechanism of acquired cancer chemoresistance. This study describes possible mechanisms, that might contribute to upregulation of ABCB1 and synergistically boost the acquisition of doxorubicin (DOX) resistance in breast cancer MX-1 cell line. DOX resistance in MX-1 cell line was induced by a stepwise increase of drug concentration or by pretreatment of cells with an ABCB1 transporter activator tetraphenylphosphonium (TPP+) followed by DOX exposure. Transcriptome analysis of derived cells was performed by human gene expression microarrays and by quantitative PCR. Genetic and epigenetic mechanisms of ABCB1 regulation were evaluated by pyrosequencing and gene copy number variation analysis. Gradual activation of canonical EMT transcription factors with later activation of ABCB1 at the transcript level was observed in DOX-only treated cells, while TPP+ exposure induced considerable activation of ABCB1 at both, mRNA and protein level. The changes in ABCB1 mRNA and protein level were related to the promoter DNA hypomethylation and the increase in gene copy number. ABCB1-active cells were highly resistant to DOX and showed morphological and molecular features of EMT. The study suggests that nongenotoxic ABCB1 inducer can possibly accelerate development of DOX resistance.

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