Integrated Profiling Identifies DXS253E As a Potential Prognostic Marker in Colorectal Cancer

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2024 Jun 18

PMID 38890691

Authors

Pu Xing

Hao Hao

Jiangbo Chen

Xiaowen Qiao

Tongkun Song

Xinying Yang

Kai Weng

Yifan Hou

Jie Chen

Zaozao Wang

Jiabo Di

Beihai Jiang

Jiadi Xing

Xiangqian Su

Affiliations

Soon will be listed here.

Abstract

Background: Increasing evidence suggests that DXS253E is critical for cancer development and progression, but the function and potential mechanism of DXS253E in colorectal cancer (CRC) remain largely unknown. In this study, we evaluated the clinical significance and explored the underlying mechanism of DXS253E in CRC.

Methods: DXS253E expression in cancer tissues was investigated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Kaplan-Meier plot was used to assess the prognosis of DXS253E. The cBioPortal, MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were employed to analyze the mutation profile, methylation, and immune infiltration associated with DXS253E. The biological functions of DXS253E in CRC cells were determined by CCK-8 assay, plate cloning assay, Transwell assay, flow cytometry, lactate assay, western blot, and qRT-PCR.

Results: DXS253E was upregulated in CRC tissues and high DXS253E expression levels were correlated with poor survival in CRC patients. Our bioinformatics analyses showed that high DXS253E gene methylation levels were associated with the favorable prognosis of CRC patients. Furthermore, DXS253E levels were linked to the expression levels of several immunomodulatory genes and an abundance of immune cells. Mechanistically, the overexpression of DXS253E enhanced proliferation, migration, invasion, and the aerobic glycolysis of CRC cells through the AKT/mTOR pathway.

Conclusions: We demonstrated that DXS253E functions as a potential role in CRC progression and may serve as an indicator of outcomes and a therapeutic target for regulating the AKT/mTOR pathway in CRC.

References

Wang B, Fan W, Tao Y, Zhang S, Wang J, Fan Z . The impact of SLC10A3 on prognosis and immune microenvironment in colorectal adenocarcinoma. Eur J Med Res. 2024; 29(1):20. PMC: 10765936. DOI: 10.1186/s40001-023-01526-4. View

Xue R, Zhang Q, Cao Q, Kong R, Xiang X, Liu H . Liver tumour immune microenvironment subtypes and neutrophil heterogeneity. Nature. 2022; 612(7938):141-147. DOI: 10.1038/s41586-022-05400-x. View

ODonnell J, Teng M, Smyth M . Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2018; 16(3):151-167. DOI: 10.1038/s41571-018-0142-8. View

Xu T, Gao H . Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?. Hum Genomics. 2020; 14(1):15. PMC: 7201531. DOI: 10.1186/s40246-020-00265-5. View

Jin L, Ge H, Long Y, Yang C, Chang Y, Mu L . CD70, a novel target of CAR T-cell therapy for gliomas. Neuro Oncol. 2017; 20(1):55-65. PMC: 5761579. DOI: 10.1093/neuonc/nox116. View

Martin N, Mount Patrick S, Estrada T, Frisk H, Rogan D, Dvorak B . Active transport of bile acids decreases mucin 2 in neonatal ileum: implications for development of necrotizing enterocolitis. PLoS One. 2011; 6(12):e27191. PMC: 3230578. DOI: 10.1371/journal.pone.0027191. View

Tian S, Li J, Xiang J, Peng P . The Clinical Relevance and Immune Correlation of SLC10 Family Genes in Liver Cancer. J Hepatocell Carcinoma. 2023; 9:1415-1431. PMC: 9809167. DOI: 10.2147/JHC.S392586. View

Ho P, Melms J, Rogava M, Frangieh C, Pozniak J, Shah S . The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity. Cancer Cell. 2023; 41(7):1207-1221.e12. PMC: 10524902. DOI: 10.1016/j.ccell.2023.05.014. View

Fernandes C, Godoy J, Doring B, Cavalcanti M, Bergmann M, Petzinger E . The novel putative bile acid transporter SLC10A5 is highly expressed in liver and kidney. Biochem Biophys Res Commun. 2007; 361(1):26-32. DOI: 10.1016/j.bbrc.2007.06.160. View

10.

Dvorak K, Watts G, Ramsey L, Holubec H, Payne C, Bernstein C . Expression of bile acid transporting proteins in Barrett's esophagus and esophageal adenocarcinoma. Am J Gastroenterol. 2009; 104(2):302-9. PMC: 4450811. DOI: 10.1038/ajg.2008.85. View

11.

Dawson P . Role of the intestinal bile acid transporters in bile acid and drug disposition. Handb Exp Pharmacol. 2010; (201):169-203. PMC: 3249407. DOI: 10.1007/978-3-642-14541-4_4. View

12.

Leek J, Johnson W, Parker H, Jaffe A, Storey J . The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28(6):882-3. PMC: 3307112. DOI: 10.1093/bioinformatics/bts034. View

13.

Geyer J, Wilke T, Petzinger E . The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships. Naunyn Schmiedebergs Arch Pharmacol. 2006; 372(6):413-31. DOI: 10.1007/s00210-006-0043-8. View

14.

Shen W, Song Z, Zhong X, Huang M, Shen D, Gao P . Sangerbox: A comprehensive, interaction-friendly clinical bioinformatics analysis platform. Imeta. 2024; 1(3):e36. PMC: 10989974. DOI: 10.1002/imt2.36. View

15.

Ma W, Mei P . SLC10A3 Is a Prognostic Biomarker and Involved in Immune Infiltration and Programmed Cell Death in Lower Grade Glioma. World Neurosurg. 2023; 178:e595-e640. DOI: 10.1016/j.wneu.2023.07.134. View

16.

Liang W, Zhao Y, Huang W, Gao Y, Xu W, Tao J . Non-invasive diagnosis of early-stage lung cancer using high-throughput targeted DNA methylation sequencing of circulating tumor DNA (ctDNA). Theranostics. 2019; 9(7):2056-2070. PMC: 6485294. DOI: 10.7150/thno.28119. View

17.

Bailey M, Tokheim C, Porta-Pardo E, Sengupta S, Bertrand D, Weerasinghe A . Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell. 2018; 173(2):371-385.e18. PMC: 6029450. DOI: 10.1016/j.cell.2018.02.060. View

18.

Laugel-Haushalter V, Bar S, Schaefer E, Stoetzel C, Geoffroy V, Alembik Y . A New Homozygous Missense Mutation Responsible for a Milder Phenotype of Skeletal Dysplasia With Amelogenesis Imperfecta. Front Genet. 2019; 10:504. PMC: 6546871. DOI: 10.3389/fgene.2019.00504. View

19.

Wang Z, Yang B, Zhang M, Guo W, Wu Z, Wang Y . lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer. Cancer Cell. 2018; 33(4):706-720.e9. PMC: 6143179. DOI: 10.1016/j.ccell.2018.03.006. View

20.

He Y, Song J, Qin Y, Mao D, Ding D, Wu S . The prognostic significance and immune correlation of SLC10A3 in low-grade gliomas revealed by bioinformatic analysis and multiple immunohistochemistry. Aging (Albany NY). 2023; 15(9):3771-3790. PMC: 10449292. DOI: 10.18632/aging.204712. View