Dataset Information

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

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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

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Project description:Although therapy responsiveness to therapy in Burkitt lymphoma (BL) is high, relapsed disease and and chemoresistance remain a clinical challenge, and complete mechanisms underlying BL chemoresistance and how it can be circumvented is yet to be fully elucidated. In this study we present data showing that chymotrypsin-like serine proteases inhibitor Nα-tosyl-L-phenylalanine chloromethylketone (TPCK) and specific NF-κB inhibitor Bay-11 7082 can induce caspase-independent apoptosis in chemoresistant BL cells. We also demonstrate that both TPCK and Bay-11 7082-treatment leads to decreased NF-κB nuclear activity and that this is associated with sensitization of chemoresistant Burkitt lymphoma cells. Furthermore we investigated global transcriptional changes induced by Bay-11 7082 and TPCK in the DG-75 and Raji cell lines, respectively, by microarray analysis using Illumina BeadChips. TPCK-treatment of Raji and DG-75 cells resulted in 59 and 21 differently expressed genes, respectively, while Bay-11-treated Raji and DG-75 cells displayed 1403 and 8 differently expressed genes, respectively. Gene Ontology (GO) categorization confirmed enrichment of multiple GOs in Bay 11-treated Raji and DG-75 cells. Fifty percent of the 61 categories in Raji cells were categories sorting under Biological Processes and represented mostly increased gene expression. In DG-75 cells Bay-11 7082 induced significant gene ontology enrichment in only two categories, where the increased/decreased ratio was 1:1. Further unsupervised and supervised bioinformatics processing by Ingenuity Pathway Analysis indicated significant networks in response to TPCK and Bay 11 respectively, including association to NF-κB. Bay-11 7082 demonstrated deregulated NF-κB related members of receptor mediated cell death signaling, i.e TRAF2 and TRADD, as well as deregulated members of the NF-κB signaling pathway from the cytoplasmic compartment, i.e RELB, in Raji cells. Comparably NF-κB network analysis of Raji- and DG-75 cells treated with Bay-11 7082 and Raji cells treated with TPCK demonstrated deregulation of NF-κB target genes CD69 and IL8. These data indicates that NF-kB may play a role in overcoming chemoresistance in BL cells with defective classical apoptosis signaling. NF-κB network analysis of Raji- and DG-75 cells treated with Bay-11 7082 and Raji cells treated with TPCK

Dataset Information

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

Publications

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

Similar Datasets

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