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Cancer

DNA Methylation-Based Patterns for Early Diagnostic Prediction and Prognostic Evaluation in Colorectal Cancer

Strategic Insights

— 1 min read

Researchers in Guangdong, People's Republic of China, have conducted a study to investigate the relationship between DNA methylation and tumor mutation burden (TMB) in colorectal cancer (CRC) patients. The study, led by Hao Huang, aimed to identify clinical benefit populations and evaluate the effect of immune checkpoint inhibitor (ICI) therapy. The research integrated genomic and epigenetic profiles of 536 CRC tissues from the Cancer Genome Atlas (TCGA) and calculated TMB levels.

Key Takeaways:

  • The study observed a positive correlation between differential methylation positions and TMB levels in the TCGA CRC cohort (r=0.45).
  • A diagnostic score consisting of methylation levels of four genes (ADHFE1, DOK6, GPR75, and MAP3K14-AS1) showed high diagnostic performance in the discovery (AUC=1.000) and two independent validation (AUC=0.946, AUC=0.857) datasets.
  • The prognostic score containing three genes (POU3F3, SYN2, and TMEM178A) had significantly poorer survival in the high-risk TMB samples than those in the low-risk TMB samples (P=0.016).
  • The study suggested that DNA methylation patterns combined with TMB serve as a novel potential biomarker for early screening in more high-TMB populations and for evaluating the prognostic effect of CRC patients with ICI therapy.
  • The research highlighted the importance of integrating analyses of methylation and mutation data for identifying clinical benefit populations.

Statistics:

  • 536 CRC tissues from the Cancer Genome Atlas (TCGA) were collected and subjected to calculate TMB levels.
  • 80 CRC patients with high TMB and paired normal tissues were selected as training sets.
  • The diagnostic model was validated in two independent datasets consisting of 47 in-house CRC tissues and 122 CRC tissues from the Gene Expression Omnibus (GEO) datasets.
  • The prognostic model was verified in 38 CRC tissues with high TMB from the COLONOMICS dataset.

Sources:

  • Huang, H., Cao, W., Long, Z., Kuang, L., Li, X., Feng, Y., Wu, Y., Zhao, Y., Chen, Y., Sun, P., Peng, P., Zhang, J., Yuan, L., Li, T., Hu, H., Li, G., Yang, L., Zhang, X., Hu, F., & Sun, X. (2022). DNA methylation-based patterns for early diagnostic prediction and prognostic evaluation in colorectal cancer patients with high tumor mutation burden. Frontiers in Oncology, 12. doi: 10.3389/fonc.2022.1030335
  • National Natural Science Foundation of China
  • Science And Technology Foundation of Shenzhen City

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