Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

CYP4F3 is associated with poor prognosis and resistance to oxaliplatin-based chemotherapy in colorectal cancer

Shifen Zhang¹ , Yuxiang Fu², Liming Liu¹, YaJie Yang³, Juan Wang⁴

¹Department of Pathology; ²Department of Gastrointestinal Surgery, Shenzhen Peopleâ€™s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology); ³Department of Pathology, Shenzhen Second Peopleâ€™s Hospital, Shenzhen 518035; ⁴Department of Radiology, Shenzhen Peopleâ€™s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.

For correspondence:- Shifen Zhang Email: shifenzhang_1635@163.com Tel:+8613420991575

Accepted: 31 January 2023 Published: 28 February 2023

Citation: Zhang S, Fu Y, Liu L, Yang Y, Wang J. CYP4F3 is associated with poor prognosis and resistance to oxaliplatin-based chemotherapy in colorectal cancer. Trop J Pharm Res 2023; 22(2):321-326 doi: 10.4314/tjpr.v22i2.14

© 2023 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To screen the expression of different genes related to oxaliplatin resistance in colorectal cancer (CRC) therapy.

Methods: Limma and principal component analysis (PCA) techniques were used to determine genes with significantly different expression levels in the Gene expression Omnibus (GEO) dataset. A lasso regression model and Venn diagram were used to analyze the intersecting genes. Gene expression Profiling Interactive Analysis (GEPIA) and the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN) online platform were used to analyze the expression of CYP4F3. The relationship between CYP4F3 expression and survival rate in colorectal cancer was analyzed by Kaplan–Meier curve, while the related pathways involving CYP4F3 were determined by Metascape and gene Ontology-Kyoto Encyclopedia of Genes and Genomes (GO-KEGG) analysis. Furthermore, the correlation between CYP4F3 and TME-related cells was analyzed by Pearson score. In addition, analysis of clinically tested and FDA-approved drugs significantly associated with CYP4F3 was carried out using CellMiner database.

Results: PCA and volcano plot analysis indicated there are four upregulated genes and 11 down-regulated genes in oxaliplatin-resistant CRC cells. The intersection gene was CYP4F3 in the lasso regression model and differentially expressed genes (DEG). Moreover, CYP4F3 was upregulated and associated with poor survival in CRC. Gene set enrichment analysis (GSEA), KEGG enrichment, and PPI analysis showed that CYP4F3 and GNG3 are the most significant genes in oxaliplatin-resistant CRC. Furthermore, CYP4F3 expression negatively correlated with the enrichment of T cells, while the expression of CYP4F3 was not associated with drug sensitivity in CRC cells.

Conclusion: The findings of this study suggest that CYP4F3 may be a target for the treatment of oxaliplatin-resistant CRC. However, the underlying mechanism of CYP4F3 in the regulation of sensitivity to oxaliplatin needs further investigation.

Keywords: Colorectal cancer, CYP4F3, Gene expression Omnibus Chip, Poor prognosis, Oxaliplatin-resistant