Frontiers in Cell and Developmental Biology (Oct 2020)

DNA Methylation-Based Panel Predicts Survival of Patients With Clear Cell Renal Cell Carcinoma and Its Correlations With Genomic Metrics and Tumor Immune Cell Infiltration

  • Xiao-Ping Liu,
  • Lingao Ju,
  • Lingao Ju,
  • Chen Chen,
  • Chen Chen,
  • Tongzu Liu,
  • Sheng Li,
  • Sheng Li,
  • Xinghuan Wang

DOI
https://doi.org/10.3389/fcell.2020.572628
Journal volume & issue
Vol. 8

Abstract

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DNA methylation based prognostic factor for patients with clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we identified survival-related DNA methylation sites based on the differentially methylated DNA CpG sites between normal renal tissue and ccRCC. Then, these survival-related DNA methylation sites were included into an elastic net regularized Cox proportional hazards regression (CoxPH) model to build a DNA methylation-based panel, which could stratify patients into different survival groups with excellent accuracies in the training set and test set. External validation suggested that the DNA methylation-based panel could effectively distinguish normal controls from tumor samples and classify patients into metastasis group and non-metastasis group. The nomogram containing DNA methylation-based panel was reliable in clinical settings. Higher total mutation number, SCNA level, and MATH score were associated with higher methylation risk. The innate immune, ratio between CD8+T cell versus Treg cell as well as Th17 cell versus Th2 cell were significantly decreased in high methylation risk group. In inclusion, we developed a DNA methylation-based panel which might be independent prognostic factor in ccRCC. Patients with higher methylation risk were associated genomic alteration and poor immune microenvironment.

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