PXD036785-2

PXD036785 is an original dataset announced via ProteomeXchange.

Title	Multi-Omics analysis revealed a significant alteration of critical metabolic pathways due to sorafenib-resistance in Hep3B cell lines
Description	Hepatocellular 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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:58:19.992.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Core Facility
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-17 02:41:50	ID requested
1	2023-01-17 00:19:46	announced
⏵ 2	2023-11-14 08:58:20	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: LC-MSMS,timsTOF, human, cells, drug-resistance

Mohammad H Semreen
contact affiliation	1 - College of Pharmacy, University of Sharjah, Sharjah 2 - Sharjah Institute for Medical Research, University of Sharjah, Sharjah
contact email	msemreen@sharjah.ac.ae
lab head
Core Facility
contact affiliation	Sharjah Institute for Medical Research, University of Sharjah
contact email	tims-tof@sharjah.ac.ae
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036785
     1. Label: PRIDE project
     2. Name: Multi-Omics analysis revealed a significant alteration of critical metabolic pathways due to sorafenib-resistance in Hep3B cell lines