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 |
MS:
| MS ID: | MS004132 |
| Analysis ID: | AN004383 |
| Instrument Name: | Bruker timsTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | MetaboScape® 4.0 software from Bruker (Bremen, Germany) was used for data processing. The parameters for the detection were as follows: a minimum of 7 spectra were used for peak detection, while for molecular features detection, the minimum intensity threshold was equivalent to 1000 counts. Mass recalibration was performed within a retention time range between 0-0.3 min. Only those features present in at least 2 of 6 samples were considered. Finally, the detected MS/MS spectra assigned onto the bucket table allowed for better viewing and understanding. The main features included retention time, measured m/z, detected fragments, and molecular weight [12]. Data bucketing parameters were as follows: the retention time range was between 0.3 min and 25 min, whereas the mass range began at 50 m/z and finished at 1,300 m/z. A two-tailed independent student’s t-test was utilized to determine the significantly altered metabolites between the two cell lines. The threshold for significance was p-value <0.05. Functional enrichment analysis was constructed utilizing the MetaboAnalyst 5.0 website (https://www.metaboanalyst.ca). |
| Ion Mode: | POSITIVE |
