Abstract
Oxaliplatin resistance is a major issue in the treatment of p53 mutant colorectal cancer (CRC). Finding the specific biomarkers would improve therapeutic efficacy of patients with CRC. In order to figure out the biomarker for CRC patients with mutant p53 access oxaliplatin, a Gene Expression Omnibus dataset (GSE42387) was used to determine differentially expressed genes (DEGs). The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software were used to predict protein-protein interactions. The Database for Annotation, Visualization, and Integrated Discovery online tool was used to group the DEGs into their common pathways. 138 DEGs were identified with 46 upregulated and 92 downregulated. In the PPI networks, 7 of the upregulated genes and 13 of the downregulated genes were identified as hub genes (high degrees). Four hub genes, aldehyde dehydrogenase 2 family member (ALDH2), aldo-keto reductase family 1 member B1 (AKR1B1), aldo-keto reductase family 1 member B10 (AKR1B10), and monoglyceride lipase (MGLL) were enriched in the most significant pathway, glycerolipid metabolism. Further, we found that low expression of ALDH2 is correlated with poor overall survival and oxaliplatin resistance. Finally, we found that combined treatment with ALDH2 inhibitor and oxaliplatin will reduce the sensitivity to oxaliplatin in p53 mutant HT29 cells. In conclusion, we demonstrate that ALDH2 may be a biomarker for oxaliplatin resistance status in CRC patients and bring new insight into treatment strategy for p53 mutant CRC patients.
Highlights
Colorectal cancer (CRC) is the most common cancer worldwide [1, 2]
P53 is the common tumor suppressor gene involved in cell cycle arrest, DNA repair, and apoptosis in cellular stress [10, 11]. p53 mutation is related to many types of cancer, and about 40 to 50% of sporadic CRC has p53 mutation which is involved in cell proliferation, migration, invasion, angiogenesis, and drug resistance of cancer [12, 13]
In order to figure out the specific target for oxaliplatin resistance in p53 mutant CRC patients, the HT29 parental and oxaliplatin-resistant data (GSE42387 dataset) which consisted of 32,701 probe sets were applied for our study
Summary
Colorectal cancer (CRC) is the most common cancer worldwide [1, 2]. Surgery followed by adjuvant chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the treatment of choice for nonmetastatic CRC [3, 4]. P53 is the common tumor suppressor gene involved in cell cycle arrest, DNA repair, and apoptosis in cellular stress [10, 11]. Finding the specific target for oxaliplatin resistance in p53 mutant CRC patients needs to be studied. Gene expression profiling of human cancers has provided important insights into mechanisms and targets implicated in oncogenesis in several cancers [20, 21]. Chronic exposure to oxaliplatin induces different gene expression patterns in several CRC cells [22]. In our study, we used HT29 cells which carried mutated p53 and predicted possible target genes in oxaliplatin resistance by bioinformatics approaches, including constructing a protein-protein interaction network, predicting hub genes and pathways, and identifying gene expressions in tumor and normal tissues and overall survival. The findings may provide new insights into oxaliplatin resistance on CRC patients carried with mutant p53
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
