Transcriptomic Profiling Reveals an Enhancer RNA Signature for Recurrence Prediction in Colorectal Cancer
Abstract
:1. Introduction
2. Results
2.1. Building Survival Model to Identify Clinically Relevant eRNAs
- We randomly selected 70% of the entire cohort from The Cancer Genome Atlas (TCGA) as the training set and reserved the remaining 30% of the cohort as the testing set. To avoid deviation affecting the stability of the model, we maintained the distribution of disease-free and relapsed patients from the entire cohort in both training and testing sets.
- Multivariate Cox regression analysis was carried out training on 477 eRNAs for CC and 460 eRNAs for RC, along with controlling the effects from other clinical risk factors, including patient age, gender, and TNM stage.
- eRNAs significantly associated (p < 0.05 & z-score > 1.96) for predicting patient disease-free survival (DFS) were retained and termed as prognostic eRNAs and were further selected by LASSO Cox regularization with 10-fold cross-validation.
- Following LASSO Cox regularization and eRNA selection, a risk score formula was established. The risk score for each patient was calculated by a linear combination of expression and multivariate Cox coefficient of eRNAs.
- Patients were classified into low-risk or high-risk groups using the median risk score as the cut-off threshold from the training set. The coefficient for each eRNA and the cut-off value of the risk score from the training set was used to calculate the risk score and to stratify patients into individual risk groups in the testing set.
- Survival differences between the two groups were estimated using Kaplan–Meier curve and compared using the log-rank test.
2.2. Prognostic Association of eRNA Signature Risk Score with Disease-Free Survival in Patients
2.3. Recurrence Prediction by eRNA Signature Is Independent of Clinical Risk Factors
2.4. The eRNA Signature Is a Better Predictor of Recurrence with High Sensitivity and Specificity
2.5. Higher Expression of eRNAs Associated with Tumor Recurrence Compared to Its Target Genes
2.6. Putative Biological Functions of eRNA Signature in Colorectal Cancer
3. Discussion
4. Conclusions
5. Methods
5.1. CRC Patients Datasets
5.2. Consensus Molecular Subtypes (CMS) Classification
5.3. Identification of Prognostic eRNAs Associated with Tumor Relapse
5.4. Risk Score Calculation
5.5. Statistical Analysis
5.6. Gene Set Enrichment Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Sahu, D.; Lin, C.-C.; Goel, A. Transcriptomic Profiling Reveals an Enhancer RNA Signature for Recurrence Prediction in Colorectal Cancer. Genes 2023, 14, 137. https://doi.org/10.3390/genes14010137
Sahu D, Lin C-C, Goel A. Transcriptomic Profiling Reveals an Enhancer RNA Signature for Recurrence Prediction in Colorectal Cancer. Genes. 2023; 14(1):137. https://doi.org/10.3390/genes14010137
Chicago/Turabian StyleSahu, Divya, Chen-Ching Lin, and Ajay Goel. 2023. "Transcriptomic Profiling Reveals an Enhancer RNA Signature for Recurrence Prediction in Colorectal Cancer" Genes 14, no. 1: 137. https://doi.org/10.3390/genes14010137
APA StyleSahu, D., Lin, C.-C., & Goel, A. (2023). Transcriptomic Profiling Reveals an Enhancer RNA Signature for Recurrence Prediction in Colorectal Cancer. Genes, 14(1), 137. https://doi.org/10.3390/genes14010137