Consequently, we found that differential-methylation and copy number alterations of STAT3/CDK2/4/6 are associated with dysfunctional T-cell phenotypes, high death risk, and short survival duration of multiple cancer cohorts, hence providing preliminary evidence for the use of STAT3/CDK2/4/6 signature for DNA methylation-based biomarkers of dysfunctional T-cell phenotypes. This evidence concerns the gene CDK2 and cancer.