Gut microbiota during tamoxifen therapy in patients with breast cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB80483 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR13927600_1.fastq.gz | Fastqsanger.gz | |||
| ERR13927600_2.fastq.gz | Fastqsanger.gz | |||
| ERR13927700_1.fastq.gz | Fastqsanger.gz | |||
| ERR13927700_2.fastq.gz | Fastqsanger.gz | |||
| ERR13927601_1.fastq.gz | Fastqsanger.gz |
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Project description:Tamoxifen, an antagonist to estrogen receptor (ER), is a first line drug used in breast cancer treatment. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying the resistance to tamoxifen, we established a tamoxifen-resistant cell line by treating the MCF7 breast cancer cell line with tamoxifen for over 6 months. We showed that this cell line exhibited resistance to tamoxifen both in vitro and in vivo. In order to quantify the phosphorylation alterations associated with tamoxifen resistance, we performed SILAC-based quantitative phosphoproteomic profiling on the resistant and vehicle-treated sensitive cell lines where we identified >5,600 unique phosphopeptides. We found phosphorylation levels of 1,529 peptides were increased (>2 fold) and 409 peptides were decreased (<0.5-fold) in tamoxifen resistant cells compared to tamoxifen sensitive cells. Gene set enrichment analysis revealed that focal adhesion pathway was the top enriched signaling pathway activated in tamoxifen resistant cells. We observed hyperphosphorylation of the focal adhesion kinases FAK1 and FAK2 in the tamoxifen resistant cells. Of note, FAK2 was not only hyperphosphorylated but also transcriptionally upregulated in tamoxifen resistant cells. Suppression of FAK2 by specific siRNA knockdown could sensitize the resistant cells to the treatment of tamoxifen. We further showed that inhibiting FAK activity using the small molecule inhibitor PF562271 repressed cellular proliferation in vitro and tumor formation in vivo. More importantly, our survival analysis revealed that high expression of FAK2 significantly associated with short metastasis-free survival of ER-positive breast cancer patients treated with tamoxifen-based hormone therapy. Our studies suggest that FAK2 is a great potential target for the development of therapy for the treatment of hormone refractory breast cancers.
2016-05-25 | PXD001812 | Pride
Project description:Tumor gene expression data (microarray from FFPE) was obtained from breast cancer patients enrolled in a pre-operative window trial (ClinicalTrials.gov Identifier: NCT00738777). Patients received an oral loading dose of 40 mg of tamoxifen twice daily for the first seven days, followed by a daily dose of 20 mg until surgery. A core needle biopsy of the tumor was taken prior to treatment (n=62) and post-treatment tumor material (n=40) was obtained during surgery 20.7 (±9.6) days later. Paired material was available for 27/74 patients. Differential analysis comparing gene expression before and after Tamoxifen treatment implicated activation of the NFκB pathway and an enrichment of EMT/stemness features upon Tamoxifen treatment. In line with these findings, exposure of ER+ breast cancer cell lines to tamoxifen, in vitro and in vivo, gives rise to a tamoxifen-tolerant population with similar NFκB activity and EMT/stemness characteristics as described in the corresponding publication.
2020-04-06 | GSE147271 | GEO
Project description:Tamoxifen is essential in treating estrogen receptor-positive (ER+) breast cancer, primarily through its active metabolite, endoxifen. Emerging research suggests potential interactions between tamoxifen and gut microbiota. This study investigates the effects of tamoxifen on gut microbiota composition in postmenopausal ER+ and human epidermal growth factor receptor 2 negative (HER2-) breast cancer patients and explores correlations between gut microbiota and endoxifen plasma levels. This prospective observational study included postmenopausal ER+/HER2- breast cancer patients. Fecal and blood samples were collected before and during 6-12 weeks of tamoxifen therapy. Gut microbiota composition was analyzed using 16S rRNA amplicon sequencing of the hypervariable V4 gene region, and plasma endoxifen levels were measured using liquid chromatography-mass spectrometry. Changes in microbial diversity and composition were assessed, with correlations to endoxifen levels. A total of 62 patients were included. Tamoxifen significantly increased microbial richness (p = 0.019), although overall community structure remained consistent between pre- and during-treatment samples. Notable changes were observed in specific microbial taxa, with significant increases in genera such as Blautia (padjusted = 0.003) and Streptococcus (padjusted = 0.010), and decreases in Prevotella_9 (padjusted = 0.006). No significant correlations between gut microbiota and endoxifen levels were identified after multiple comparisons. Tamoxifen therapy increases gut microbial diversity in postmenopausal ER+/HER2- breast cancer patients, though overall microbial community structure remains stable. The absence of significant correlations with endoxifen levels suggests that while tamoxifen affects the gut microbiota, its role in endoxifen metabolism requires further study. More comprehensive research is needed to understand the relationship between tamoxifen, gut microbiota, and therapeutic outcomes.
| S-EPMC11885672 | biostudies-literature
Project description:56 estrogen receptor positive breast cancer tissues from patients treated with tamoxifen upon recurrence (32 Good outcome vs 24 Poor outcome) have been microdissected to obtain a pure population of epithelial tumor cells. Breast tumor enriched tissues have been sonicated and proteins have been in-solution digested and analyzed via a LTQ-Orbitrap coupled online with a nano-LC system. Thermo output .RAW files were analyzed through MaxQuant (version 1.4.1.2) using the human proteome FASTA (version 2012-09, human canonical proteome) as search library.
2015-08-21 | PXD000484 | Pride
Project description:56 Estrogen Receptor Positive Breast cancer tissues coming from patients treated with tamoxifen upon recurrence (41 Good outcome vs 15 Poor outcome) have been microdissected to enrich for breast cancer tumor cells. Enriched tissue has been lysed and proteins digested and analyzed in an LTQ-Orbitrap coupled online with a Dionex nLC system. Thermo output .RAW files were analyzed through MaxQuant (version 1.4.1.2) using the human proteome FASTA (version 2012-09, human canonical proteome) as search library. LFQ parameters in MaxQuant have been enabled (Fast LFQ) and other settings have been kept as default.
2015-08-21 | PXD000485 | Pride
Project description:Classification of tamixifen-treated breast cancer patients into high and low risk groups using the 76-gene signature Experiment Overall Design: 136 breast cancer samples that were treated with tamoxifen were classified using the 76-gene signature
2008-10-26 | E-GEOD-12093 | biostudies-arrayexpress
Project description:dataset of 60 patients with ER-positive primary breast cancer and treated with tamoxifen monotherapy for 5 years. Data were generated from LCMed cancer cells. Sample_keyword: breast cancer, tamoxifen, recurrence Keywords: other
2004-06-07 | GSE1378 | GEO
Project description:Purpose: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence. Experimental design: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by 2 independent test sets (N=60 and N=40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.
2012-04-19 | GSE37405 | GEO
Project description:dataset of 60 patients with ER-positive primary breast cancer and treated with tamoxifen monotherapy for 5 years. Data were generated from whole tissue sections of breast cancers. Sample_keyword: breast cancer, tamoxifen, recurrence Keywords: other
2004-06-07 | GSE1379 | GEO
Project description:Long-term tamoxifen treatment significantly improves the survival of hormone receptor-positive (HR+) breast cancer (BC) patients. However, tamoxifen resistance remains a big challenge for endocrine therapy. We aimed to identify prognostic biomarkers for tamoxifen treatment and explore their role in tamoxifen resistance. We used Exiqon miRCURY™ LNA Array (v.18.0) to detect the miRNA expression profiles in the primary tumors and their matched recurrent/metastatic lesions from six HR+ breast cancer patients who relapsed after TAM treatment. Fold changes ≥ 2 and P values < 0.05 were defined as differential expression. We found that 28 miRNAs were significantly downregulated in recurrent/metastatic lesions compared to primary tumors, and 54 miRNAs were significantly upregulated.
2016-12-29 | GSE83292 | GEO