Summary of Study ST002703
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 PR001674. The data can be accessed directly via it's Project DOI: 10.21228/M8B14V 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 | ST002703 |
| Study Title | Multi-Omics Analysis Revealed a Significant Molecular Changes in Doxorubicin-Resistant Lung Cancer Cells. |
| Study Type | LC/MS/MS |
| Study Summary | Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy resistance in lung cancer is one of the major characteristics of an aggressive phenotype with poor prognosis. Therefore, there is a critical need to explore the significant molecular changes associated with resistance to conventional chemotherapy, and identify potential therapeutic targets for treatment of resistant lung cancer. In this study, we have performed comprehensive quantitative proteomics and metabolomics analysis of non-small cell lung cancer cells (A549-P) and doxorubicin resistant A549 cells (A549-R), using state-of-the-art Trapped Ion Mobility Spectroscopy, Time-of-Flight Mass Spectrometry (TIMS-TOF-MS). The results revealed 30 dysregulated proteins and 37 significantly altered metabolites in A549-R cells compared to A549-P cells. Among the significantly upregulated proteins are liver carboxylesterase 1, anterior gradient protein 2 homolog and nicotinamide phosphoribosyltransferase. A group of the upregulated proteins are endogenous and xenobiotic-metabolizing enzymes, including UDP-glucuronosyltransferase 1-6, CES1, and epoxide hydrolase 1. While Importin, ATP-citrate synthase and CTP synthase are downregulated. The significantly altered metabolites include sepiapterin, glutathione, glycine, pyridine and niacinamide. The performed multi-omics integrated analysis revealed the involvement of purine and glutathione metabolism, ABC transporters, citric acid cycle in the development of resistance in A549 cells, besides the involvement of energy metabolism, pathways related to cancer progression, invasion and migration, and redox homeostasis. Collectively, this exploratory study effectively revealed the significantly dysregulated proteins and metabolites in doxorubicin resistant A549 cells and shed the light on potential biomarkers for chemotherapy resistant non-small cell lung cancer. In addition, multi-omics integrated analysis elucidates the involved pathways in resistance including pathways related to progression and invasion which would improve prognosis and open the door for new potential therapeutic targets. |
| Institute | University of Sharjah |
| Department | Research institute of medical and health science |
| Laboratory | Biomarker Discovery Group |
| Last Name | Facility |
| First Name | Core |
| Address | M32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah, Sharjah, UAE, Sharjah, 000, United Arab Emirates |
| tims-tof@sharjah.ac.ae | |
| Phone | +971 6 5057656 |
| Submit Date | 2023-05-04 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-11-30 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004383 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Bruker timsTOF |
| Column | Hamilton Intensity Solo 2 C18(100 x 2.1 mm, 1.8 um) |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Bruker timsTOF |
| Ion Mode | POSITIVE |
| Units | AU |
Chromatography:
| Chromatography ID: | CH003288 |
| Chromatography Summary: | Then, liquid chromatography separation was done using Intensity Solo 1.8 C18-2 column (100×2.1 mm, 1.8 μm) from Bruker Daltonik GmbH (Bremen, Germany). The column temperature was kept at 35 ℃ and the flow rate was constant at 0.3 ml/min. The mobile phase composed of 0.1% FA in HPLC grade water (solvent A) and 0.1% FA in ACN (solvent B). |
| Instrument Name: | Bruker timsTOF |
| Column Name: | Hamilton Intensity Solo 2 C18(100 x 2.1 mm, 1.8 um) |
| Column Temperature: | 35 |
| Flow Gradient: | 1% B was held for 2 min, ramping to 99% B over 15 min, and held at 99% B for 3 min before re-equilibrating to 1% B for 10 min |
| Flow Rate: | 250 uL/min |
| Solvent A: | Water (0.1% Formic Acid) |
| Solvent B: | ACN (0.1% Formic Acid) |
| Chromatography Type: | Reversed phase |
