scholarly journals Network-based approach to identify biomarkers predicting response and prognosis for HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7515 ◽  
Author(s):  
Cui Jiang ◽  
Shuo Wu ◽  
Lei Jiang ◽  
Zhichao Gao ◽  
Xiaorui Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Treatment ◽  
Signaling Pathway ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Breast Cancer Treatment ◽  
Chemotherapeutic Response ◽  
Ppar Signaling

Objective This study aims to identify effective gene networks and biomarkers to predict response and prognosis for HER2-negative breast cancer patients who received sequential taxane-anthracycline neoadjuvant chemotherapy. Materials and Methods Transcriptome data of training dataset including 310 HER2-negative breast cancer who received taxane-anthracycline treatment and an independent validation set with 198 samples were analyzed by weighted gene co-expression network analysis (WGCNA) approach in R language. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were performed for the selected genes. Module-clinical trait relationships were analyzed to explore the genes and pathways that associated with clinicopathological parameters. Log-rank tests and COX regression were used to identify the prognosis-related genes. Results We found a significant correlation of an expression module with distant relapse–free survival (HR = 0.213, 95% CI [0.131–0.347], P = 4.80E−9). This blue module contained genes enriched in biological process of hormone levels regulation, reproductive system, response to estradiol, cell growth and mammary gland development as well as pathways including estrogen, apelin, cAMP, the PPAR signaling pathway and fatty acid metabolism. From this module, we further screened and validated six hub genes (CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2), the expression of which were significantly associated with both better chemotherapeutic response and favorable survival for BC patients. Conclusion We used WGCNA approach to reveal a gene network that regulate HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy, which enriched in pathways of estrogen signaling, apelin signaling, cAMP signaling, the PPAR signaling pathway and fatty acid metabolism. In addition, genes of CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2 might serve as novel biomarkers predicting chemotherapeutic response and prognosis for HER2-negative breast cancer.

scholarly journals ETV5 Regulates Hepatic Fatty Acid Metabolism Through PPAR Signaling Pathway

Diabetes ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 214-226
Author(s):  
Zhuo Mao ◽  
Mingji Feng ◽  
Zhuoran Li ◽  
Minsi Zhou ◽  
Langning Xu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Signaling Pathway ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Hepatic Fatty Acid ◽  
Ppar Signaling

scholarly journals ETV5 regulates hepatic fatty acid metabolism through PPAR signaling pathway

2020 ◽  
Author(s):  
Ada Admin ◽  
Zhuo Mao ◽  
Mingji Feng ◽  
Zhuoran Li ◽  
Minsi Zhou ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Association Studies ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Alcoholic Fatty Liver ◽  
Hepatic Fatty Acid ◽  
Ppar Signaling

ETV5 is an ETS transcription factor which has been associated with obesity in genomic association studies. However, little is known about the role of ETV5 in hepatic lipid metabolism and non-alcoholic fatty liver disease (NAFLD). In the present study, we found that ETV5 protein expression was increased in diet- and genetic-induced steatotic liver. ETV5 responded to the nutrient status in an mTORC1 dependent manner and in turn regulated mTORC1 activity. Both viral-mediated and genetic depletion of ETV5 in mice led to increased lipid accumulation in the liver. RNA sequencing analysis revealed that PPAR signaling and fatty acid degradation/metabolism pathways were significantly downregulated in ETV5 deficient hepatocytes <i>in vivo</i> and <i>in vitro. </i>Mechanistically, ETV5 could bind to the PPRE region of PPAR downstream genes and enhance its transactivity. Collectively, our study identifies ETV5 as a novel transcription factor for the regulation of hepatic fatty acid metabolism which is required for the optimal β oxidation process. ETV5 may provide a therapeutic target for the treatment of hepatic steatosis.<br>

scholarly journals Fatty acid synthase promotes breast cancer metastasis by mediating changes in fatty acid metabolism

2020 ◽  
Vol 21 (1) ◽  
pp. 1-1
Author(s):  
Shuo Xu ◽  
Tingting Chen ◽  
Lihua Dong ◽  
Tao Li ◽  
Hui Xue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthase ◽  
Cancer Metastasis ◽  
Acid Metabolism ◽  
Breast Cancer Metastasis

Fatty acid metabolism in breast cancer cells: differential inhibitory effects of epigallocatechin gallate (EGCG) and C75

2007 ◽  
Vol 109 (3) ◽  
pp. 471-479 ◽  
Author(s):  
Teresa Puig ◽  
Alejandro Vázquez-Martín ◽  
Joana Relat ◽  
Jordi Pétriz ◽  
Javier A. Menéndez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Metabolism ◽  
Breast Cancer Cells ◽  
Acid Metabolism ◽  
Epigallocatechin Gallate ◽  
Inhibitory Effects

scholarly journals Acyl-CoA Medium-Chain Synthetase-3 Promotes Chemosensitivity of Ovarian Cancer through the Inhibition of PI3K/AKT Signaling Pathway

2021 ◽  
Author(s):  
Yuanyuan An ◽  
Hua Duan
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Immune Status ◽  
Akt Signaling ◽  
Ovarian Cancer Cells ◽  
Akt Signaling Pathway

Abstract Introduction: Dysregulation of fatty acid metabolism often occurs in tumor, which mainly constitutes of fatty acid synthesis and oxidation. In recent years, studies found that fatty acid metabolism participated in regulation of tumor immune microenvironment, which further influenced the progress of cancer. Thus, it is important to explore the key fatty acid metabolism-related molecules, which not only affects the prognosis of ovarian cancer, but also shows a close correlation with immune microenvironment of cancer.Methods: Database from TCGA was used to explore the fatty acid metabolism-related molecules, which correlated with the prognosis of ovarian cancer using univariate and multivariate cox proportional regression model. Nomogram was constructed to predict the prognostic probability based on ACSM3 and clinicopathological parameters. GDSC database was used to investigate the chemosensitivity of ovarian cancer cells. The correlation between ACSM3 and immune status of ovarian cancer was analyzed by TIMER and TISIDB online tools. In addition, CCK8 assay was used to investigate the chemosensitivity of ovarian cancer cells, real time-PCR and western blot were used to investigate the expression of chemoresistance-related genes.Results: ACSM3 worked as an independent favorable prognostic molecule through univariate and multivariate cox regression analysis. For the use in clinical, nomogram was constructed, and higher expression of ACSM3 showed better prognosis. We found that ACSM3 could regulate PI3K/AKT signaling, and GDSC database showed that PI3K/AKT inhibitor could promote the chemosensitivity of ovarian cancer cells. In addition, the expression of ACSM3 showed significantly correlated with the immune status of ovarian cancer. In vitro experiments showed that ACSM3 can promote the chemosensitivity of ovarian cancer cells by inhibiting PI3K/AKT signaling pathway.Conclusion: Our results showed that ACSM3 acted as a favorable prognostic-related biomarker for ovarian cancer, which could promote chemosensitivity of ovarian cancer through inhibiting PI3K/AKT signaling pathway. This might be due to participate in regulating immune status of ovarian cancer microenvironment.

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