Mutations conferring differential treatment response in breast cancer
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ABSTRACT:
PROVIDER: EGAS00001003626 | EGA |
REPOSITORIES: EGA
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Project description:This experiment is designed to screen miRNAs that are deregulated during chemoresistance-associated metastasis of lung cancer cells. Chemoresistant metastatic in vivo tumor model of A549-luc-Vector cells was established after four rounds of cisplatin (CDDP) treatments compared to corresponding control solvent treatments. Upon examining profiles of miRNA expression differential between tumor-derived cultured cells from the Ctrl-4th and CDDP-4th treatments, most markedly upregulated and downregulated miRNAs in chemoresistant, metastatic A549-luc-CDDP-4th cells were identified. In order to establish a chemoresistant in vivo tumor model, after inoculation of A549-luc-Vector cells, cisplatin (CDDP) or control solvent was intraperitoneally (i.p.) injected six rounds in a two-week period and cells were isolated from corresponding resultant tumors, cultured and re-transplanted into syngeneic mice to receive the next round of treatment. In our experimental model, human lung cancer xenografts developed chemoresistance in the third round of CDDP treatment (CDDP-3rd) and chemoresistance-associated metastases following the fourth round of treatment. Tumor-derived cultured cells from Ctrl-4th and CDDP (cisplatin)-4th treatment were subjected to miRNA array (Agilent-031181 human miRNA (8*60k) V16.0) analysis, with two biological replications for each treatment.
2015-04-10 | E-GEOD-67727 | biostudies-arrayexpress
Project description:Goal of the experiment Recurrence is a frequent phenomenon in intracranial childhood ependymomas. To understand this process, we investigated whether the gene expression profiling of matched ependymomas at diagnosis and at relapse could reveal key molecular events involved in tumor progression. To gain new insight in this process and identify pathways associated with recurrence, we compared the gene expression profiles of local recurrences with the corresponding initial tumors. Brief description We analyzed 17 tumor samples at diagnosis and a total of 27 paired recurrences. Recurrences analyzed occurred after surgery only in 12 cases, surgery plus chemotherapy only in 9 cases and any treatment plus radiotherapy in 6 cases. We compared the level of gene expression for each tumor at recurrence relative to its expression at diagnosis using Agilent 44K dual color gene expression microarrays.
2010-12-31 | E-TABM-873 | biostudies-arrayexpress
Project description:Chemoresistance is a major cause of poor prognosis of breast cancer.More and more mRNAs and lncRNAs are reported to upregulate chemoresistance in breast cancer.To explore the how mRNAs and lncRNAs involved in chemoresistance of breast cancer,we sceened upregulated mRNAs and lncRNA from parental MCF-7 , chemoresistant MCF-7 cells as well as 4 breast cancer tissue sensitive to chemotherapy and 4 resistant to chemotherapy . Total RNA was extracted using Trizol reagent. Agilent Human lncRNA Microarray V6 (4*180K) was used to analyze the global profiling of human lncRNAs and protein-coding transcripts in these samples. The microarray contains 83,835 lncRNAs and 27,233 coding genes.
2020-02-25 | E-MTAB-8787 | biostudies-arrayexpress
Project description:Identification of specific risk groups for recurrence after surgery for colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic and predictive value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after surgery for CRLM. Methods: Tumour samples of CRLM from two patient groups were collected: I) patients with recurrent disease within 12 months after surgery (N=33), and II) patients without recurrences and disease free for at least 36 months (N=30). The included patients were clinically homogeneous; all patients had a low risk profile (clinical risk score 0-2) and did not receive (neo-) adjuvant chemotherapy. Extracted total RNA from both groups was hybridized to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a potentially prognostic gene expression signature. Results: The LOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease within 12 months after partial hepatectomy. This gene expression profile had a sensitivity of 81.8%, with a specificity of 66.7% for predicting early recurrences (within 12 months) versus no recurrences for at least 36 months after surgery (X2 P<0.0001). Conclusion: The current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.
2017-01-01 | GSE81423 | GEO
Project description:Chemoresistance frequently leads to therapeutic failure in tongue squamous cell carcinoma (TSCC). Increasing evidence has shown that Long noncoding RNAs (lncRNAs) play pivotal roles in biological properties of cancer. However, the roles and mechanisms of lncRNAs in cisplatin resistance are not well understood. In this study, to identify the lncRNAs induced by chemotherapy, we profile the expression of lncRNAs in cisplatin-resistant TSCC cells using LncRNA microarrays.
2018-06-12 | GSE115119 | GEO
Project description:Goal of the experiment : Recurrence is a frequent phenomenon in intracranial childhood ependymomas. To understand this process, we investigated whether the gene expression profiling of matched ependymomas at diagnosis and at relapse could reveal key molecular events involved in tumor progression. To gain new insight in this process and identify mechanisms associated with recurrence, we compared the CGH profiles of local recurrences with the corresponding initial tumors. Brief description We analyzed 17 tumor samples at diagnosis and a total of 27 paired recurrences. Recurrences analyzed occurred after surgery only in 12 cases, surgery plus chemotherapy only in 9 cases and any treatment plus radiotherapy in 6 cases. We compared the level of CGH profile for each tumor at diagnosis and recurrence relative to normal commercial DNA using Agilent 4x44K Human CGH microarrays.
2011-06-20 | E-TABM-1023 | biostudies-arrayexpress
Project description:Neoadjuvant chemotherapy (NAC) is the major pre-treatment for breast cancer before surgery. Patients who achieve pathologic complete response (pCR) have a higher chance to receive lumpectomy and a better quality of life after neoadjuvant treatment. Luminal subtype breast cancer has poor NAC response compared with triple-negative breast cancer (TNBC) subtype. The molecular and cellular mechanisms underlying this chemoresistance are not fully understood. Here we report that the 17 featured transcriptional factors (TFs) in luminal and TNBC were identified. The association between 17 TFs and NAC pCR were analysis and exogenous luminal featured TF GATA3 overexpression promotes chemotherapy resistance in TNBC cell lines whereas its knockdown promotes sensitivity. In mechanism, we found that anthracycline based chemotherapy induces robust cellular ROS and Fe2+ overload in sensitivity cells; GATA3 mediates cell survival through repress CYB5R2 expression and Fenton reducing in DOX recycle which reduce cellular ROS and Fe2+ level during chemotherapy procedure. These founding altogether indicate that luminal featured transcription factor GATA3 enhance NAC resistance thorough repress ROS production and Fenton reducing. Breast cancer patient with GATA3 high expression might not suit for anthracycline based NAC regimen.
2023-01-01 | GSE216413 | GEO
Project description:The tumor microenvironment (TME) plays an important role in tumorigenesis1. The TME is usually studied in tumor tissue and in relation to tumor progression2,3, which can limit understanding of how the TME is involved in processes associated with initial tumorigenesis as well as tumor recurrence and metastasis after surgery. To describe the underlying mechanisms of human hepatocellular carcinoma (HCC) occurrence and progression, we propose a new concept, the peritumor microenvironment (PME). We collected normal (all biochemical indicators of liver function, imaging examination and histopathology examination were normal) and peritumor (The liver tissues adjacent to the tumor were approximately 2 cm away from the tumor and were taken from patients with HCC who did not receive tumor radiotherapy, tumor chemotherapy or targeted drug therapy before surgery) to perform a proteomic characterization of the PME in peritumor liver tissues.
2022-02-22 | PXD023118 | Pride
Project description:Acquired resistance of chronic lymphocytic leukemia (CLL) to chemotherapy is an important clinical problem and is often caused by cytogenetic aberrations or gene mutations affecting the ATM-p53 DNA damage response pathway or other pathways. However, there are also a lot of resistant cases without detectable mutations and we decided to check whether there are specific epigenetic changes at the level of DNA methylation that might underlie resistance development in CLL. We used Illumina Infinium HumanMethylation450 BeadChips to obtain DNA methylation profiles of 71 CLL patients with different responses to chemotherapy. Fifty-one patients were subjects of the CLL2O clinical trial and 36 of them were categorized as relapsed/refractory after treatment with fludarabine- or bendamustine-containing regimens, whereas the other 15 patients as well as 20 additional patients not on the trial were untreated at the time of sampling. Although we could not correlate chemoresistance with epigenetic changes, we believe that the dataset is valuable and can be used by researchers to test other hypotheses, especially as the patients are well characterized regarding different prognostic and molecular markers (IGHV mutation status, chromosome aberrations, TP53 mutation status, etc.).
2020-03-13 | GSE136724 | GEO
Project description:<p>Overcoming resistance to chemotherapies remains a major unmet need for cancers such as triple negative breast cancer (TNBC). Therefore, mechanistic studies to provide insight for drug development are urgently needed to overcome TNBC therapy resistance. Recently, an important role of fatty acid β-Oxidation (FAO) in chemoresistance has been shown. But how FAO might mitigate tumor cell apoptosis by chemotherapy is unclear. Here, we show that elevated FAO activates STAT3 by acetylation via elevated acetyl-CoA. Acetylated STAT3 upregulates expression of long-chain acyl-CoA synthetase 4 (ACSL4), resulting in increased phospholipid synthesis. Elevating phospholipids in mitochondrial membranes leads to heightened mitochondrial integrity, which in turn overcomes chemotherapy-induced tumor cell apoptosis. Conversely, in both cultured tumor cells and xenograft tumors, enhanced cancer cell apoptosis by inhibiting ASCL4 or specifically targeting acetylated-STAT3 is associated with a reduction in phospholipids within mitochondrial membranes. This study demonstrates a critical mechanism underlying tumor cell chemoresistance.</p>
2022-05-31 | MTBLS4709 | MetaboLights