Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Label Free Quantification Mass Spectrometry Identifies Protein Markers of Chemoresistance in Serous Ovarian Cancer

ABSTRACT: Ovarian cancer is still the most lethal gynecological cancer, despite advances in patients’ strati-fication and treatment. Only about 80% of patients respond to the first line of treatment and many suffer a relapse with a treatment resistant disease. Here, we have identified three potential markers for chemoresistance using primary tumour samples. Moreover, we have shown their concurrent regulation in a chemoresistant cell line. This implies those cells as a useful model to study chemoresistance and to test novel drugs.

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oocyte

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Parul Mittal

LAB HEAD: Prof Peter Hoffmann

PROVIDER: PXD033785 | Pride | 2023-05-10

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	1.mgf	Mgf
	141030_Transition_Results_from_run_141002.csv	Csv
	173.mgf	Mgf
	173_analysis.baf	Other
	1_analysis.baf	Other

Items per page:

1 - 5 of 57

Publications

Label-Free Quantification Mass Spectrometry Identifies Protein Markers of Chemotherapy Response in High-Grade Serous Ovarian Cancer.

Arentz Georgia G Mittal Parul P Klingler-Hoffmann Manuela M Condina Mark R MR Ricciardelli Carmela C Lokman Noor A NA Kaur Gurjeet G Oehler Martin K MK Hoffmann Peter P

Cancers 20230406 7

Eighty percent of ovarian cancer patients initially respond to chemotherapy, but the majority eventually experience a relapse and die from the disease with acquired chemoresistance. In addition, 20% of patients do not respond to treatment at all, as their disease is intrinsically chemotherapy resistant. Data-independent acquisition nano-flow liquid chromatography-mass spectrometry (DIA LC-MS) identified the three protein markers: gelsolin (GSN), calmodulin (CALM1), and thioredoxin (TXN), to be e ...[more]

PMID: 37046833

Similar Datasets

Small RNA-sequencing of bone marrow samples from acute myeloid leukemia patients chemoresistant (n=27) versus chemosensitive (n=20).

Project description:The aim of our research project is to identify microRNAs involved in chemoresistance in acute myeloid leukemia patients. We performed small RNA-sequencing on baseline bone marrow samples and compared chemoresistant versus chemosensitive patient samples.

2021-02-11 | E-MTAB-8775 | biostudies-arrayexpress

Antagonizing miR-128 abrogates chemoresistance-associated metastasis and is therapeutic in non-small cell lung cancer [miRNA]

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

Genome-wide profiling of long noncoding RNA expression patterns in chemoresistant breast cancer cells

Project description:Long non-coding RNAs (lncRNAs) are involved in cancer progression. In this study, the lncRNA profiling were analyzed in chemoresistant and sensitive breast cancer cells. We found a group of dysregulated lncRNAs in chemoresistant cells. Expression of dysregulated lncRNAs are correlated with dysregulated mRNAs, and enriched in GO and KEGG pathways related with cancer progression and chemoresistance development. Within those lncRNA-mRNA interactions, some lncRNAs may cis-regulate neighboring protein coding genes and involved in chemoresistance. The lncRNA NONHSAT028712 was then validated to regulate nearby CDK2 and interfere with cell cycle and chemoresistance. Furthermore, we identified another group of lncRNAs trans-regulated gene expression via interacting with different transcription factors (TF). Whereby NONHSAT057282 and NONHSAG023333 was found to modulate chemoresistance and most likely interacted with ELF1 and E2F1 respectively. In conclusion, this study reported for the first time the lncRNA expression patterns in chemoresistant breast cancer cells, and provided a group of novel lncRNA targets in mediating chemoresistance development in both cis- and trans- action mode. MCF-7/ADM replication 3 times, MCF-7/WT replication 3 times

2016-05-28 | E-GEOD-81971 | biostudies-arrayexpress

The non-apoptotic function of Caspase-8 in negatively regulating the CDK9 mediated Ser2 phosphorylation of RNA Polymerase II in cervical cancer

Project description:Cervical cancer is the fourth most frequently diagnosed and fatal gynecological cancer. 15-61% of all cases metastasize and develop chemoresistance, reducing the 5-year survival of cervical cancer patients to as low as 17%. Therefore, unraveling the mechanisms contributing to metastasis is critical in developing better-targeted therapies against it. Here, we have identified a novel mechanism where nuclear Caspase-8 directly interacts with and inhibits the activity of CDK9, thereby modulating RNAPII-mediated global transcription, including those of cell-migration and -invasion-associated genes. Crucially, low Caspase-8 expression in cervical cancer patients leads to poor prognosis, higher CDK9 phosphorylation at Thr186, and increased RNAPII activity in cervical cancer cell lines and patient biopsies. Caspase-NT8 knock-out cells were also more resistant to the small-molecule CDK9 inhibitor BAY1251152 in both 2D- and 3D-culture conditions. Combining BAY1251152 with Cisplatin synergistically overcame chemoresistance of Caspase-8 deficient cervical cancer cells. Therefore, Caspase-8 expression could be a marker in chemoresistant cervical tumors, suggesting CDK9 inhibitor treatment for their sensitization to Cisplatin-based chemotherapy.

2023-03-11 | PXD038102 | Pride

Acquired semi-squamalization during chemotherapy suggests a differentiation therapy for bladder cancer

Project description:Cisplatin-based chemotherapy is the most common treatment for unresectable bladder cancers and also increasingly used as neoadjuvant treatments before or after surgery and radiotherapy. Unfortunately, though many patients respond to the treatment, most of them develop resistance quickly with unclear mechanisms and few further treatment options. Here, we report that semi-squamazation is acquired during chemo treatment in both mice and human. Multi-omics analyses show that cathepsin H (CTSH), a direct target of p63, is associated with chemoresistance and semi-squamation. Treatment with the cathepsin inhibitor E64 specifically restrains chemoresistant but not chemosensitive cancer. Mechanistically, cathepsin inhibition induces fully squamous differentiation of bladder cancer cells, which requires TNF receptor 1alpha and is associated with pyroptosis. Our study suggests that semi-squamazation would be a diagnosistic marker for chemoresistance and differentiation therapy by targeting CTSH might be a potential treatment for chemoresistant bladder cancer.

2022-07-09 | GSE192575 | GEO

Genome-wide profiling of long noncoding RNA expression patterns in chemoresistant breast cancer cells

2016-05-28 | GSE81971 | GEO

Chemoresistant Cancer Cell Lines are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations.

Project description:Chemoresistance remains the major barrier to effective ovarian cancer treatment. The molecular features and associated biological functions of this phenotype remain poorly understood. We developed carboplatin resistant cell line models using OVCAR5 and CaOV3 cell lines with the aim of identifying chemoresistance-specific molecular features. Chemotaxis and CAM invasion assays revealed enhanced migratory and invasive potential in OVCAR5 resistant, compared to parental cells lines. Mass spectrometry analysis was used to analyse the metabolome and proteome of these cell lines and was able to separate these populations based on their molecular features. It revealed signalling and metabolic perturbations in chemoresistant cell lines. Comparison with the proteome of patient derived primary ovarian cancer cells grown in culture showed a shared dysregulation of cytokine and type 1 interferon signalling, potentially revealing a common molecular feature of chemoresistance. A comprehensive analysis of a larger patient cohort, including advanced in vitro and in vivo models, promises to help better understand the molecular mechanisms of chemoresistance and associated enhancement of migration and invasion.

2022-08-11 | PXD034246 | Pride

Upregulated mRNAs and lncRNAs in chemoresistant breast cancer

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

Transcriptomic analysis of DOXO-Resistant cells compared to parental DOXO-Sensitive mda-mb-436 cell line

Project description:The major obstacle in successfully treating triple negative breast cancer (TNBC) is resistance to cytotoxic chemotherapy, the mainstay of treatment in this disease. Previous pre-clinical models of chemoresistance in TNBC have suffered from a lack of clinical relevance. Using a single high dose chemotherapy treatment, we developed a novel MDA-MB-436 cell-based model of chemoresistance characterized by a unique and complex morphological phenotype, which consists of polyploid giant cancer cells (PGCCs) giving rise to neuron-like mononuclear daughter cells filled with smaller but functional mitochondria and numerous lipid droplets. This resistant phenotype is associated with metabolic reprogramming with a shift to a greater dependence on fatty acids and oxidative phosphorylation. We validated both the molecular and histologic features of this model in a clinical cohort of primary chemoresistant TNBCs and identified several metabolic vulnerabilities including a dependence on PLIN4, a perilipin coating the observed lipid droplets, expressed both in the TNBC resistant cells and clinical chemoresistant tumors treated with neoadjuvant doxorubicin-based chemotherapy. These findings thus reveal a novel mechanism of chemotherapy resistance that has therapeutic implications in the treatment of drug resistant cancer.

2019-11-30 | GSE138233 | GEO

Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection

Project description:Chemotherapy-resistant cancer recurrence is a major cause of mortality. In acute myeloid leukemia (AML), chemorefractory relapses result from the complex interplay between altered genetic, epigenetic and transcriptional states in leukemic cells. We developed an experimental model system using in vitro lineage tracing coupled with exome, transcriptome and in vivo functional readouts to assess the AML population dynamics and associated molecular determinants underpinning chemoresistance development. We found that combining standard chemotherapeutic regimens with low doses of DNA methyltransferase inhibitors (DNMTi, hypomethylating drugs) prevents chemoresistant relapses. Mechanistically, DNMTi suppressed the outgrowth of a pre-determined set of chemoresistant AML clones with stemness properties, instead favoring the expansion of rarer and unfit chemosensitive clones. Importantly, we confirmed the capacity of DNMTi combination to suppress stemness-dependent chemoresistance development in both xenotransplantation models and primary AML patient samples. Together, these results support the potential of DNMTi combination treatment to circumvent the development of chemorefractory AML relapses.

2019-07-19 | GSE134506 | GEO