Document Type
Article
Publication Date
12-13-2023
Publication Title
Scientific Reports
Volume
13
First page number:
1
Last page number:
19
Abstract
Colorectal cancer (CRC) involves epigenetic alterations. Irregular gene-methylation alteration causes and advances CRC tumor growth. Detecting differentially methylated genes (DMGs) in CRC and patient survival time paves the way to early cancer detection and prognosis. However, CRC data including survival times are heterogeneous. Almost all studies tend to ignore the heterogeneity of DMG effects on survival. To this end, we utilized a sparse estimation method in the finite mixture of accelerated failure time (AFT) regression models to capture such heterogeneity. We analyzed a dataset of CRC and normal colon tissues and identified 3406 DMGs. Analysis of overlapped DMGs with several Gene Expression Omnibus datasets led to 917 hypo- and 654 hyper-methylated DMGs. CRC pathways were revealed via gene ontology enrichment. Hub genes were selected based on Protein–Protein-Interaction network including SEMA7A, GATA4, LHX2, SOST, and CTLA4, regulating the Wnt signaling pathway. The relationship between identified DMGs/hub genes and patient survival time uncovered a two-component mixture of AFT regression model. The genes NMNAT2, ZFP42, NPAS2, MYLK3, NUDT13, KIRREL3, and FKBP6 and hub genes SOST, NFATC1, and TLE4 were associated with survival time in the most aggressive form of the disease that can serve as potential diagnostic targets for early CRC detection.
Controlled Subject
Colon (Anatomy)--Cancer; Cancer--Research; DNA--Analysis
Disciplines
Genetic Processes | Medical Genetics | Medical Pathology
File Format
File Size
3900 KB
Language
English
Rights
IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Repository Citation
Hajebi Khaniki, S., Shokoohi, F., Esmaily, H. et al. Analyzing aberrant DNA methylation in colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients. Sci Rep 13, 22104 (2023). https://doi-org/10.1038/s41598-023-47377-1