Gene set enrichment analysis provides insight into novel signalling pathways in breast cancer stem cells

Background. We analyzed the n6-methyladenosine (m6A) modification patterns of immune cells infiltrating the tumor microenvironment of breast cancer (BC) to provide a new perspective for the early diagnosis and treatment of BC. Methods. Based on 23 m6A regulatory factors, we identified m6A-related gene characteristics and m6A modification patterns in BC through unsupervised cluster analysis. To examine the differences in biological processes among various m6A modification modes, we performed genomic variation analysis. We then quantified the relative infiltration levels of different immune cell subpopulations in the tumor microenvironment of BC using the CIBERSORT algorithm and single-sample gene set enrichment analysis. Univariate Cox analysis was used to screen for m6A characteristic genes related to prognosis. Finally, we evaluated the m6A modification pattern of patients with a single BC by constructing the m6Ascore based on principal component analysis. Results. We identified three different m6A modification patterns in 2128 BC samples. A higher abundance of the immune infiltration of the m6Acluster C was indicated by the results of CIBERSORT and the single-sample gene set enrichment analysis. Based on the m6A characteristic genes obtained through screening, the m6Ascore was determined. The BC patients were segregated into m6Ascore groups of low and high categories, which revealed significant survival benefits among patients with low m6Ascores. Additionally, the high-m6Ascore group had a higher mutation frequency and was associated with low PD-L1 expression, and the m6Ascore and tumor mutation burden showed a positive correlation. In addition, treatment effects were better in patients in the high-m6Ascore group. Conclusions. In case of a single patient with BC, the immune cell infiltration characteristics of the tumor microenvironment and the m6A methylation modification pattern could be evaluated using the m6Ascore. Our results provide a foundation for improving personalized immunotherapy of BC.

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Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer

Cancer Cell International ◽

10.1186/s12935-019-0986-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 17

Author(s):

Jingbo Sun ◽

Jingzhan Huang ◽

Jin Lan ◽

Kun Zhou ◽

Yuan Gao ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Western Blot ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Free Survival ◽

Gene Set ◽

Oncomine Database ◽

Kaplan Meier

Abstract Background Centromere Protein F (CENPF) associates with the centromere–kinetochore complex and influences cell proliferation and metastasis in several cancers. The role of CENPF in breast cancer (BC) bone metastasis remains unclear. Methods Using the ONCOMINE database, we compared the expression of CENPF in breast cancer and normal tissues. Findings were confirmed in 60 BC patients through immunohistochemical (IHC) staining. Microarray data from GEO and Kaplan–Meier plots were used analyze the overall survival (OS) and relapse free survival (RFS). Using the GEO databases, we compared the expression of CENPF in primary lesions, lung metastasis lesions and bone metastasis lesions, and validated our findings in BALB/C mouse 4T1 BC models. Based on gene set enrichment analysis (GSEA) and western blot, we predicted the mechanisms by which CENPF regulates BC bone metastasis. Results The ONCOMINE database and immunohistochemical (IHC) showed higher CENPF expression in BC tissue compared to normal tissue. Kaplan–Meier plots also revealed that high CENPF mRNA expression correlated to poor survival and shorter progression-free survival (RFS). From BALB/C mice 4T1 BC models and the GEO database, CENPF was overexpressed in primary lesions, other target organs, and in bone metastasis. Based on gene set enrichment analysis (GSEA) and western blot, we predicted that CENPF regulates the secretion of parathyroid hormone-related peptide (PTHrP) through its ability to activate PI3K–AKT–mTORC1. Conclusion CENPF promotes BC bone metastasis by activating PI3K–AKT–mTORC1 signaling and represents a novel therapeutic target for BC treatment.

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High TNFRSF12A level associated with MMP-9 overexpression is linked to poor prognosis in breast cancer: Gene set enrichment analysis and validation in large-scale cohorts

PLoS ONE ◽

10.1371/journal.pone.0202113 ◽

2018 ◽

Vol 13 (8) ◽

pp. e0202113 ◽

Cited By ~ 9

Author(s):

Jungho Yang ◽

Kyueng-Whan Min ◽

Dong-Hoon Kim ◽

Byoung Kwan Son ◽

Kyoung Min Moon ◽

...

Keyword(s):

Breast Cancer ◽

Poor Prognosis ◽

Large Scale ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Cancer Gene ◽

Gene Set Enrichment ◽

Gene Set ◽

Breast Cancer Gene

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Insight into the Candidate Genes and Enriched Pathways Associated with Height, Length, Length to Height Ratio and Body-Weight of Korean Indigenous Breed, Jindo Dog Using Gene Set Enrichment-Based GWAS Analysis

Animals ◽

10.3390/ani11113136 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3136

Author(s):

Sunirmal Sheet ◽

Jong-Seok Kim ◽

Min-Jeong Ko ◽

Na-Yeon Kim ◽

Young-Jo Lim ◽

...

Keyword(s):

Body Weight ◽

Candidate Genes ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Potential Candidate ◽

Height Ratio ◽

Gene Set Enrichment ◽

Gene Set ◽

A Genome ◽

Insight Into

As a companion and hunting dog, height, length, length to height ratio (LHR) and body-weight are the vital economic traits for Jindo dog. Human selection and targeted breeding have produced an extraordinary diversity in these traits. Therefore, the identification of causative markers, genes and pathways that help us to understand the genetic basis of this variability is essential for their selection purposes. Here, we performed a genome-wide association study (GWAS) combined with enrichment analysis on 757 dogs using 118,879 SNPs. The genomic heritability (h2) was 0.33 for height and 0.28 for weight trait in Jindo. At p-value < 5 × 10−5, ten, six, thirteen and eleven SNPs on different chromosomes were significantly associated with height, length, LHR and body-weight traits, respectively. Based on our results, HHIP, LCORL and NCAPG for height, IGFI and FGFR3 for length, DLK1 and EFEMP1 for LHR and PTPN2, IGFI and RASAL2 for weight can be the potential candidate genes because of the significant SNPs located in their intronic or upstream regions. The gene-set enrichment analysis highlighted here nine and seven overlapping significant (p < 0.05) gene ontology (GO) terms and pathways among traits. Interestingly, the highlighted pathways were related to hormone synthesis, secretion and signalling were generally involved in the metabolism, growth and development process. Our data provide an insight into the significant genes and pathways if verified further, which will have a significant effect on the breeding of the Jindo dog’s population.

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