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 |
|---|---|
| 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 |
Chromatography:
| Chromatography ID: | CH002752 |
| Chromatography Summary: | The Elute UHPLC and Q-TOF Mass Spectrometer (Bruker, Bremen, Germany) were utilized for metabolite and peptide detection. The Elute HPG 1300 pumps, Elute Au-tosampler (Bruker, Bremen, Germany), and Hamilton® Intensity Solo 2 C18 column (100 mm x 2.1 mm, 1.8 m beads) were employed using reversed-phase chromatog-raphy. Solvents used for separation were 0.1 % FA in LC grade water (solvent A) and 0.1 % FA in ACN (solvent B). Each metabolite and protein extract were analyzed in duplicate. For metabolomics analysis, the column was kept at 35°C, and each sample was injected twice with an in-jection volume of 10 µL. Sample elution was performed in 30 min gradient starting with 1% ACN for 2 min and then ramped to 99% ACN within 15 min. After that, 99% ACN was kept for 3 min, and then the re-equilibration to 1% ACN was done for 10 min. The flow rate was 0.25 mL/min for 20 min and then 0.35 mL/min for 8.3 min and then the flow rate set at 0.25 mL/min for 1.7 min. |
| Instrument Name: | UHPLC-QTOF-MS |
| Column Name: | Hamilton Intensity Solo 2 C18 (100 mm x 2.1 mm,1.8um) |
| Column Temperature: | 35°C |
| Flow Gradient: | Sample elution was performed in 30 min gradient starting with 1% ACN for 2 min and then ramped to 99% ACN within 15 min. After that, 99% ACN was kept for 3 min, and then the re-equilibration to 1% ACN was done for 10 min |
| Flow Rate: | was 0.25 mL/min for 20 min and then 0.35 mL/min for 8.3 min and then the flow rate set at 0.25 mL/min for 1.7 min. |
| Solvent A: | 100% water; 0.1% formic acid |
| Solvent B: | 100% acetonitrile; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
