scholarly journals Leptin Signaling Affects Survival and Chemoresistance of Estrogen Receptor Negative Breast Cancer

2020 ◽  
Vol 21 (11) ◽  
pp. 3794 ◽  
Author(s):  
Crystal C. Lipsey ◽  
Adriana Harbuzariu ◽  
Robert W. Robey ◽  
Lyn M. Huff ◽  
Michael M. Gottesman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Leptin Receptor ◽  
Patient Survival ◽  
The Cancer Genome Atlas ◽  
Leptin Signaling ◽  
Cancer Genome Atlas ◽  
Targeted Gene Expression ◽  
Estrogen Receptor Negative

Estrogen-receptor-negative breast cancer (BCER−) is mainly treated with chemotherapeutics. Leptin signaling can influence BCER− progression, but its effects on patient survival and chemoresistance are not well understood. We hypothesize that leptin signaling decreases the survival of BCER− patients by, in part, inducing the expression of chemoresistance-related genes. The correlation of expression of leptin receptor (OBR), leptin-targeted genes (CDK8, NANOG, and RBP-Jk), and breast cancer (BC) patient survival was determined from The Cancer Genome Atlas (TCGA) mRNA data. Leptin-induced expression of proliferation and chemoresistance-related molecules was investigated in triple-negative BC (TNBC) cells that respond differently to chemotherapeutics. Leptin-induced gene expression in TNBC was analyzed by RNA-Seq. The specificity of leptin effects was assessed using OBR inhibitors (shRNA and peptides). The results show that OBR and leptin-targeted gene expression are associated with lower survival of BCER− patients. Importantly, the co-expression of these genes was also associated with chemotherapy failure. Leptin signaling increased the expression of tumorigenesis and chemoresistance-related genes (ABCB1, WNT4, ADHFE1, TBC1D3, LL22NC03, RDH5, and ITGB3) and impaired chemotherapeutic effects in TNBC cells. OBR inhibition re-sensitized TNBC to chemotherapeutics. In conclusion, the co-expression of OBR and leptin-targeted genes may be used as a predictor of survival and drug resistance of BCER− patients. Targeting OBR signaling could improve chemotherapeutic efficacy.

scholarly journals SEMA6D Expression and Patient Survival in Breast Invasive Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Dongquan Chen ◽  
Yufeng Li ◽  
Lizhong Wang ◽  
Kai Jiao
Keyword(s):  
Breast Cancer ◽  
Expression Profile ◽  
Heart Development ◽  
Invasive Carcinoma ◽  
Patient Survival ◽  
The Cancer Genome Atlas ◽  
Breast Cancer Patients ◽  
Genomic Expression ◽  
Cancer Genome Atlas ◽  
Public Datasets

Breast cancer (BC) is the second most common cancer diagnosed in American women and is also the second leading cause of cancer death in women. Research has focused heavily on BC metastasis. Multiple signaling pathways have been implicated in regulating BC metastasis. Our knowledge of regulation of BC metastasis is, however, far from complete. Identification of new factors during metastasis is an essential step towards future therapy. Our labs have focused on Semaphorin 6D (SEMA6D), which was implicated in immune responses, heart development, and neurogenesis. It will be interesting to know SEMA6D-related genomic expression profile and its implications in clinical outcome. In this study, we examined the public datasets of breast invasive carcinoma from The Cancer Genome Atlas (TCGA). We analyzed the expression of SEMA6D along with its related genes, their functions, pathways, and potential as copredictors for BC patients’ survival. We found 6-gene expression profile that can be used as such predictors. Our study provides evidences for the first time that breast invasive carcinoma may contain a subtype based on SEMA6D expression. The expression of SEMA6D gene may play an important role in promoting patient survival, especially among triple negative breast cancer patients.

scholarly journals Adipocyte hypoxia promotes epithelial-mesenchymal transition-related gene expression and estrogen receptor-negative phenotype in breast cancer cells

2015 ◽  
Vol 33 (6) ◽  
pp. 2689-2694 ◽  
Author(s):  
AIWEI YAO-BORENGASSER ◽  
BEHJATOLAH MONZAVI-KARBASSI ◽  
REBECCA A HEDGES ◽  
LORA J ROGERS ◽  
SUSAN A KADLUBAR ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Related Gene ◽  
Mesenchymal Transition ◽  
Estrogen Receptor Negative ◽  
Negative Phenotype

scholarly journals Gene expression trend changes in breast cancer populations over two decades: insights from The Cancer Genome Atlas database

2021 ◽  
Author(s):  
Jinbo Wu ◽  
Taobo Hu ◽  
Shu Wang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Viral Myocarditis ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Venn Diagram ◽  
Cancer Etiology ◽  
Term Survival ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Background: Breast cancer has remained the most common malignancy in women over the past two decades. As lifestyle and living environments have changed, alterations to the disease spectrum have inevitably occurred in this time. As molecular profiling has become a routine diagnostic and objective indicator of breast cancer etiology, we analyzed changes in gene expression in breast cancer populations over two decades using The Cancer Genome Atlas (TCGA). Methods: We performed Heatmap and Venn diagram analyses to identify constantly up- and down-regulated genes in this cohort. We used Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to visualize associated functional pathways. Results: We determined that three oncogenes, PD-L2, ETV5, and MTOR and 113 long intergenic non-coding RNAs (lincRNAs) were constantly up-regulated, whereas two oncogenes, BCR and GTF2I, one tumor suppression gene (TSG) MEN1, and 30 lincRNAs were constantly down-regulated. Up-regulated genes were enriched in “focal adhesion” and “PI3K-Akt signaling” pathways, et al, and down-regulated genes were significantly enriched in “metabolic pathways” and “viral myocarditis”. Eight up-regulated genes exhibited doubled or higher expression, and the expression of three down-regulated genes was halved or lowered and correlated with long-term survival. Conclusions: In this study, we determined that genes and molecular pathways are constantly changing, importantly, some altered genes were associated with prognostics and are potential therapeutic targets, suggesting molecular typing technologies must keep pace with this dynamic situation.

scholarly journals Gene expression trend changes in breast cancer populations over two decades: insights from The Cancer Genome Atlas database

2021 ◽  
Author(s):  
jinbo wu ◽  
Taobo Hu ◽  
shu wang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Viral Myocarditis ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Venn Diagram ◽  
Cancer Etiology ◽  
Term Survival ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Background Breast cancer has remained the most common malignancy in women over the past two decades. As lifestyle and living environments have changed, alterations to the disease spectrum have inevitably occurred in this time. As molecular profiling has become a routine diagnostic and objective indicator of breast cancer etiology, we analyzed changes in gene expression in breast cancer populations over two decades using The Cancer Genome Atlas (TCGA). Methods We performed Heatmap and Venn diagram analyses to identify constantly up- and down-regulated genes in this cohort. We used Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to visualize associated functional pathways. Results We determined that three oncogenes, PD-L2, ETV5, and MTOR and 113 long intergenic non-coding RNAs (lincRNAs) were constantly up-regulated, whereas two oncogenes, BCR and GTF2I, one tumor suppression gene (TSG) MEN1, and 30 lincRNAs were constantly down-regulated. Up-regulated genes were enriched in “focal adhesion” and “PI3K-Akt signaling” pathways, et al, and down-regulated genes were significantly enriched in “metabolic pathways” and “viral myocarditis”. Eight up-regulated genes exhibited doubled or higher expression, and the expression of three down-regulated genes was halved or lowered and correlated with long-term survival. Conclusions In this study, we determined that genes and molecular pathways are constantly changing, importantly, some altered genes were associated with prognostics and are potential therapeutic targets, suggesting molecular typing technologies must keep pace with this dynamic situation.

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