Summary of Study ST002273
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001454. The data can be accessed directly via it's Project DOI: 10.21228/M8S71T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST002273 |
Study Title | Multi-Omics analysis revealed a significant alteration of critical metabolic pathways due to sorafenib-resistance in Hep3B cell lines |
Study Type | MS- comparative metabolomic analysis |
Study Summary | 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. |
Institute | Sharjah Institute for Medical Research |
Last Name | Soares |
First Name | Nelson |
Address | University of Sharjah, Sharjah, UAE |
nsoares@sharjah.ac.ae | |
Phone | +971 65 05 7763 |
Submit Date | 2022-08-31 |
Raw Data Available | Yes |
Raw Data File Type(s) | d |
Analysis Type Detail | LC-MS |
Release Date | 2022-09-16 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN003715 |
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Analysis type | MS |
Chromatography type | Reversed phase |
Chromatography system | UHPLC-QTOF-MS |
Column | Hamilton Intensity Solo 2 C18 (100 mm x 2.1 mm,1.8um) |
MS Type | ESI |
MS instrument type | Trapped Ion Mobility Q-TOF |
MS instrument name | Bruker timsTOF |
Ion Mode | POSITIVE |
Units | AU |
MS:
MS ID: | MS003464 |
Analysis ID: | AN003715 |
Instrument Name: | Bruker timsTOF |
Instrument Type: | Trapped Ion Mobility Q-TOF |
MS Type: | ESI |
MS Comments: | For MS2 acquisition in metabolomics analysis, the collision energy was fluctuated between 100-250% of 20 eV and end plate offset of 500V. The acquisition was in two sections: auto MS scan for the calibrant sodium formate in 0-0.3 min, and auto MS/MS for fragmentation, in 0.3 to 30 min. Positive mode at 12 Hz was performed in both acquisition sections . The scan range was 20 to 1300 m/z, the precursor ion’s width of ±0.5, the precursors number of 3 , the cycle time of 0.5 s econds, and the threshold of 400 counts. After three spectra, active exclusion was performed and released after 0.2 min. A timsTOF (Bruker, Bremen, Germany) with an Apollo II electrospray ionization (ESI) source was utilized for the MS analysis with the following parameters: the nebulizer pressure was 2.2 bar, the drying gas flow rate was 10 L/min, the drying tempera-ture was 220°C, and the capillary voltage was 4500 V. In the first 0.3 min of each LC-MS/MS run, the external cali-brant, sodium formate, was injected. Mass calibration was done prior to analysis ac-cording to the manufacturer’s recommendations using external mass calibration (10 mM sodium formate calibrant solution). The performance of the column and the mass spectrometer was tested using a test mixture of (TRX-2101/RT-28-calibrants for Bruker T-ReX LC-QTOF solution from Nova Medical Testing Inc.) to check the performance of reversed-phase liquid chromatography (RPLC) separation and perform multipoint re-tention time calibration, and (TRX-3112-R/MS Certified Human serum for Bruker T-ReX LC-QTOF solution from Nova Medical Testing Inc.) to check the performance of sample preparation protocols as well as LC-MS instruments. This product is prepared from pooled human blood. |
Ion Mode: | POSITIVE |