scholarly journals Integrated Analysis of Key Differentially Expressed Genes Identifies DBN1 as a Predictive Marker of Response to Endocrine Therapy in Luminal Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1549 ◽  
Author(s):  
Lutfi H. Alfarsi ◽  
Rokaya El Ansari ◽  
Brendah K. Masisi ◽  
Ruth Parks ◽  
Omar J Mohammed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Prognostic Marker ◽  
Differentially Expressed Genes ◽  
Personalised Medicine ◽  
Differentially Expressed ◽  
Endocrine Treatment ◽  
Integrated Analysis ◽  
Luminal Breast Cancer ◽  
Potential Biomarker

Endocrine therapy is the mainstay of adjuvant treatment for patients with luminal breast cancer. Despite ongoing advances in endocrine therapy to date, a proportion of patients ultimately develop endocrine resistance, resulting in failure of therapy and poor prognosis. Therefore, as part of the growing concept of personalised medicine, the need for identification of predictive markers of endocrine therapy response at an early stage, is recognised. The METABRIC series was used to identify differentially expressed genes (DEGs) in term of response to adjuvant endocrine therapy. Drebrin 1 (DBN1) was identified as a key DEG associated with response to hormone treatment. Next, large, well-characterised cohorts of primary luminal breast cancer with long-term follow-up were assessed at the mRNA and protein levels for the value of DBN1 as a prognostic marker in luminal breast cancer, as well as its potential for predicting the benefit of endocrine therapy. DBN1 positivity was associated with aggressive clinicopathological variables and poor patient outcomes. Importantly, high DBN1 expression predicted relapse patients who were subject to adjuvant endocrine treatment. Our results further demonstrate that DBN1 is an independent prognostic marker in luminal breast cancer. Its association with the response to endocrine therapy and outcome provides evidence for DBN1 as a potential biomarker in luminal breast cancer, particularly for the benefit of endocrine treatment. Further functional investigations into the mechanisms underlying sensitivity to endocrine therapy is required.

scholarly journals FABP7 is a potential biomarker to predict response to neoadjuvant chemotherapy for breast cancer

2020 ◽  
Author(s):  
Qin Xie ◽  
Ying-sheng XIAO ◽  
Shi-cheng JIA ◽  
Jie-xuan ZHENG ◽  
Zhen-chao DU ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Differentially Expressed Genes ◽  
Western Blotting ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Chemotherapeutic Regimen ◽  
Potential Biomarker ◽  
Response To Neoadjuvant Chemotherapy

Abstract Background: Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients. Methods: Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism. Results: Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease CDH1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. Conclusion: FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

scholarly journals FABP7 is a potential biomarker to predict response to neoadjuvant chemotherapy for breast cancer 

2020 ◽  
Author(s):  
Qin Xie ◽  
Ying-sheng XIAO ◽  
Shi-cheng JIA ◽  
Jie-xuan ZHENG ◽  
Zhen-chao DU ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Differentially Expressed Genes ◽  
Western Blotting ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Chemotherapeutic Regimen ◽  
Potential Biomarker ◽  
Response To Neoadjuvant Chemotherapy

Abstract Background: Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients.Methods: Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism.Results: Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease CDH1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. Conclusion: FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

scholarly journals FABP7 is a potential biomarker to predict response to neoadjuvant chemotherapy for breast cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qin Xie ◽  
Ying-sheng Xiao ◽  
Shi-cheng Jia ◽  
Jie-xuan Zheng ◽  
Zhen-chao Du ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Differentially Expressed Genes ◽  
Western Blotting ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Chemotherapeutic Regimen ◽  
Potential Biomarker ◽  
Response To Neoadjuvant Chemotherapy

Abstract Background Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients. Methods Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism. Results Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease Cdh1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. Conclusion FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

scholarly journals Investigation of Candidate Genes and Pathways in Basal/TNBC Patients by Integrated Analysis

2021 ◽  
Vol 20 ◽  
pp. 153303382110195
Author(s):  
Qi Liu ◽  
Xiang Song ◽  
Zhaoyun Liu ◽  
Zhiyong Yu
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Breast Cancer Cell Lines ◽  
Integrated Analysis ◽  
Transcription Activator ◽  
Luminal Type

Purpose: This study aims to identify the key pathway and related genes and to further explore the potential molecular mechanisms of triple negative breast cancer (TNBC). Methods: The transcriptome data and clinical information of breast cancer patients were downloaded from the TCGA database, including 94 cases of paracancerous tissue, 225 cases of Basal like type, 151 cases of Her2 type, 318 cases of Luminal type A, 281 cases of Luminal type B, and 89 cases of Normal Like type. The differentially expressed genes (DEGs) were identified based on the criteria of |logFC|≥1.5 and adjust P < 0.001.Their functions were annotated by gene ontology (GO) analysis and Kyoto Encyclopedia of differentially expressed genes & Genomes (KEGG) pathway analysis. Cox regression univariate analysis and Kaplan-Meier survival curves (Log-rank method) were used for survival analysis. FOXD1, DLL3 and LY6D were silenced in breast cancer cell lines, and cell viability was assessed by CCK-8 assay. Further, the expression of FOXD1, DLL3 and LY6D were explored by immunohistochemistry on triple negative breast tumor tissue and normal breast tissue. Results: A total of 533 DEGs were identified. Functional annotation showed that DEGs were significantly enriched in intermediate filament cytoskeleton, DNA−binding transcription activator activity, epidermis development, and Neuroactive ligand−receptor interaction. Survival analysis found that FOXD1, DLL3, and LY6D showed significant correlation with the prognosis of patients with the Basal-like type ( P < 0.05). CCK-8 assay showed that compared with Doxorubicin alone group, the cytotoxicity of Doxorubicin combined with siRNA-knockdown of FOXD1, DLL3, or LY6D was much significant. Conclusion: The DEGs and their enriched functions and pathways identified in this study contribute to the understanding of the molecular mechanisms of TNBC. In addition, FOXD1, DLL3, and LY6D may be defined as the prognostic markers and potential therapeutic targets for TNBC patients.

scholarly journals FABP7 is a potential biomarker to predict response to neoadjuvant chemotherapy for breast cancer

2020 ◽  
Author(s):  
Qin Xie ◽  
Ying-sheng XIAO ◽  
Shi-cheng JIA ◽  
Jie-xuan ZHENG ◽  
Zhen-chao DU ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Differentially Expressed Genes ◽  
Western Blotting ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Chemotherapeutic Regimen ◽  
Potential Biomarker ◽  
Response To Neoadjuvant Chemotherapy

Abstract Background Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers that could predict the response to neoadjuvant chemotherapy for breast cancer patients. Methods Three genomic profiles acquired by polymerase chain reaction (PCR) from subjects with or without residual tumors after NAC that downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to confirm the function of FABP7 in BC cells and examine the relevant mechanism. Results Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes chemotherapy for breast cancer. FABP7 is associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at GO/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease CDH1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. Conclusion FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

scholarly journals SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in estrogen receptor-positive breast cancer

2021 ◽  
Author(s):  
Lutfi H. Alfarsi ◽  
Rokaya El Ansari ◽  
Madeleine L. Craze ◽  
Omar J. Mohammed ◽  
Brendah K. Masisi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Endocrine Therapy ◽  
Predictive Marker ◽  
Amino Acid Transporter ◽  
Endocrine Treatment ◽  
Metabolic Enzyme ◽  
Luminal Breast Cancer ◽  
Acid Transporter

Abstract Purpose Identification of effective biomarkers for the benefit of endocrine treatment and understanding the molecular pathways that contribute to the development of resistance are of crucial importance to the management of luminal breast cancer. The amino acid transporter SLC1A5 has emerging importance as a prognostic marker and potential therapeutic target in various types of cancer. This study aims to investigate its role in luminal breast cancer as a potential predictive marker for endocrine treatment. Methods SLC1A5 expression was assessed at the transcriptomic and proteomic levels in large, well-characterized cohorts of luminal breast cancer. The sensitivity to endocrine therapy after SLC1A5 knockdown was investigated in vitro, using MCF7 and MDA-MB-175 cell lines. Bioinformatic analyses were performed to study the interacting networks of SLC1A5 and to identify a key co-expressed gene with SLC1A5. Results Here, we showed that patients with tumors that highly expressed SLC1A5 associated with a high risk of relapse after endocrine treatment. In vitro, depletion of SLC1A5 increases the sensitivity of luminal breast cancer cells to tamoxifen. TALDO1 was identified as key co-expressed gene with SLC1A5, and in vitro knockdown of SLC1A5 showed reduction in TALDO1 expression. Indeed, TALDO1 was associated with poor clinical outcomes in patients who were subject to endocrine therapy. Conclusion These findings suggest that metabolic alterations, particularly the interaction between the key amino acid transporter SLC1A5 and metabolic enzyme TALDO1, could affect the sensitivity of endocrine therapy. This study demonstrated the prognostic value of both SLC1A5 and TALDO1 as biomarkers in luminal breast cancer.

Endocrine Treatment of Breast Cancer: Current Perspectives, Future Directions

2017 ◽  
Vol 8 (03) ◽  
Author(s):  
Tazia Irfan ◽  
Mainul Haque ◽  
Sayeeda Rahman ◽  
Russell Kabir ◽  
Nuzhat Rahman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Premenopausal Women ◽  
New Drugs ◽  
Effective Control ◽  
Endocrine Treatment ◽  
Estrogen Production ◽  
Hormone Sensitive

Breast cancer remains one of the major causes of death in women, and endocrine treatment is currently one of the mainstay of treatment in patients with estrogen receptor positive breast cancer. Endocrine therapy either slows down or stops the growth of hormone-sensitive tumors by blocking the body’s capability to yield hormones or by interfering with hormone action. In this paper, we intended to review various approaches of endocrine treatments for breast cancer highlighting successes and limitations. There are three settings where endocrine treatment of breast cancer can be used: neoadjuvant, adjuvant, or metastatic. Several strategies have also been developed to treat hormone-sensitive breast cancer which include ovarian ablation, blocking estrogen production, and stopping estrogen effects. Selective estrogen-receptor modulators (SERMs) (e.g. tamoxifen and raloxifene), aromatase inhibitors (AIs) (e.g. anastrozole, letrozole and exemestane), gonadotropin-releasing hormone agonists (GnRH) (e.g. goserelin), and selective estrogen receptor downregulators (SERDs) (e.g. fulvestrant) are currently used drugs to treat breast cancer. Tamoxifen is probably the first targeted therapy widely used in breast cancer treatment which is considered to be very effective as first line endocrine treatment in previously untreated patients and also can be used after other endocrine therapy and chemotherapy. AIs inhibit the action of enzyme aromatase which ultimately decrease the production of estrogen to stimulate the growth of ER+ breast cancer cells. GnRH agonists suppress ovarian function, inducing artificial menopause in premenopausal women. Endocrine treatments are cheap, well-tolerated and have a fixed single daily dose for all ages, heights and weights of patients. Endocrine treatments are not nearly as toxic as chemotherapy and frequent hospitalization can be avoided. New drugs in preliminary trials demonstrated the potential for improvement of the efficacy of endocrine therapy including overcoming resistance. However, the overall goals for breast cancer including endocrine therapy should focus on effective control of cancer, design personalized medical therapeutic approach, increase survival time and quality of life, and improve supportive and palliative care for end-stage disease.

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