AUTHOR=Feng Zhongsheng , Liu Zhanju , Peng Kangsheng , Wu Wei 

TITLE=A Prognostic Model Based on Nine DNA Methylation-Driven Genes Predicts Overall Survival for Colorectal Cancer

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.779383

DOI=10.3389/fgene.2021.779383

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Colorectal cancer (CRC) is the third most frequently diagnosed malignancy and the fourth leading cause of cancer-related death among common tumors in the world. We aimed to establish and validate a risk assessment model to predict overall survival (OS) for the CRC patients.</p><p><bold>Methods:</bold> DNA methylation-driven genes were identified by integrating DNA methylation profile and transcriptome data from The Cancer Genome Atlas (TCGA) CRC cohort. Then, a risk score model was built based on LASSO, univariable Cox and multivariable Cox regression analysis. After analyzing the clinicopathological factors, a nomogram was constructed and assessed. Another cohort from GEO was used for external validation. Afterward, the molecular and immune characteristics in the two risk score groups were analyzed.</p><p><bold>Results:</bold> In total, 705 methylation-driven genes were identified. Based on the LASSO and Cox regression analyses, nine genes, i.e., <italic>LINC01555</italic>, <italic>GSTM1</italic>, <italic>HSPA1A</italic>, <italic>VWDE</italic>, <italic>MAGEA12</italic>, <italic>ARHGAP</italic>, <italic>PTPRD</italic>, <italic>ABHD12B</italic> and <italic>TMEM88</italic>, were selected for the development of a risk score model. The Kaplan–Meier curve indicated that patients in the low-risk group had considerably better OS (<italic>P</italic> = 2e-08). The verification performed in subgroups demonstrated the validity of the model. Then, we established an OS-associated nomogram that included the risk score and significant clinicopathological factors. The concordance index of the nomogram was 0.81. A comprehensive molecular and immune characteristics analysis showed that the high-risk group was associated with tumor invasion, infiltration of immune cells executing pro-tumor suppression (such as myeloid-derived suppressor cells, regulatory T cells, immature dendritic cells) and higher expression of common inhibitory checkpoint molecules (ICPs).</p><p><bold>Conclusion:</bold> Our nine-gene associated risk assessment model is a promising signature to distinguish the prognosis for CRC patients. It is expected to serve as a predictive tool with high sensitivity and specificity for individualized prediction of OS in the patients with CRC.</p>