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PXD036785-2

PXD036785 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMulti-Omics analysis revealed a significant alteration of critical metabolic pathways due to sorafenib-resistance in Hep3B cell lines
DescriptionHepatocellular carcinoma (HCC) is the second prominent cause of cancer-associated death worldwide. Usually, HCC is diagnosed in advanced stages, where sorafenib, a multiple target ty-rosine kinase inhibitor, is used as the first line of treatment. Unfortunately, resistance to sorafenib is usually encountered within six months of the treatment. Therefore, there is a critical need to identify the underlying reasons for drug resistance. In the present study, we investigated the proteomic and metabolomics alterations accompanying to sorafenib resistance in hepatocellular carcinoma Hep3B cells by employing ultra-high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS). The Bruker Human Metabolome Database (HMDB) library was used to identify the differentially abundant metabolites through MetaboScape 4.0 software (Bruker). For protein annotation and identification, the Uniprot proteome for Homo sapiens (Human) da-tabase was utilised through MaxQuant. The results revealed that 27 metabolites and 18 proteins were significantly dysregulated due to sorafenib resistance in Hep3B cells compared to the parental phenotype. D-alanine, L-proline, o-tyrosine, succinic acid and phosphatidylcholine (PC, 16:0/16:0) were among the significantly altered metabolites. Ubiquitin carboxyl-terminal hydrolase isozyme L1, mitochondrial superoxide dismutase, UDP-glucose-6-dehydrogenase, sorbitol dehydrogenase and calpain small subunit 1 were among the significantly altered proteins. The findings revealed that resistant Hep3B cells demonstrated significant alterations in amino acid and nucleotide met-abolic pathways, energy production pathways and other pathways related to cancer aggressive-ness, migration, proliferation, and drug-resistance. Joint pathway enrichment analysis unveiled unique pathways, including the antifolate resistance pathway and other important pathways that maintain cancer cells' survival, growth, and proliferation. Collectively, the results identified po-tential biomarkers for sorafenib-resistant HCC and gave insights into their role in chemotherapeutic drug resistance, cancer initiation, progression, and aggressiveness, which may contribute to better prognosis and chemotherapeutic outcomes.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:58:19.992.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterCore Facility
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-09-17 02:41:50ID requested
12023-01-17 00:19:46announced
22023-11-14 08:58:20announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: LC-MSMS,timsTOF, human, cells, drug-resistance
Contact List
Mohammad H Semreen
contact affiliation1 - College of Pharmacy, University of Sharjah, Sharjah 2 - Sharjah Institute for Medical Research, University of Sharjah, Sharjah
contact emailmsemreen@sharjah.ac.ae
lab head
Core Facility
contact affiliationSharjah Institute for Medical Research, University of Sharjah
contact emailtims-tof@sharjah.ac.ae
dataset submitter
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Dataset FTP location
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