Study Supports Use of Methylated DNA Biomarkers for Cancer Diagnosis and Prognosis

A recent study added weight to the theory that methylated DNA biomarkers could be used for cancer diagnosis and prognosis.

Methylation is a biological process by which methyl groups are added to a DNA molecule. This modification can change the activity of a DNA segment without changing the nucleotide sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and cancer development.

In a recent study, investigators at the H. Lee Moffitt Cancer Center & Research Institute (Tampa, FL, USA) introduced the concept of tumor-based expression quantitative trait methylation (eQTM), which could correlate with gene methylation patterns and gene expression to identify potential biomarkers. For this study, the investigators worked with melanoma as a disease model and assessed whether it was possible to identify a particular methylation signature that could interpret the nature of a tumor’s immune environment and could predict patient outcomes.

Results revealed that methylation sequences in melanoma samples could serve as a surrogate biomarker for the cytolytic activity score (CYT - an index of cancer immunity calculated from the mRNA expression levels of the granzyme A and perforin genes) and predict the type of immune environment in a tumor. In particular, they showed that methylation of the TCF7 (transcription factor 7) gene could predict whether T-cells in a tumor had anti-tumor properties. Furthermore, the TCF7 signature combined with the cytolytic activity score predicted patient outcomes. Melanoma patients with a low TCF7 signature and a high cytolytic activity score had longer survival times than did patients with other signature combinations.

Senior author Dr. Xuefeng Wang, associate member of the department of biostatistics and bioinformatics at the H. Lee Moffitt Cancer Center & Research Institute, said, “While additional studies need to be performed, these analyses suggest that determining immunoepignomic status through tumor-based expression quantitative trait methylation screening could allow for an accurate prediction of patient outcomes. The discovery unlocks potential new targets for personalized treatment decisions. It is similar to a fingerprint or iris scan, as featured in the cover art for the journal.”

The study was published as the cover article in the May 3, 2020, issue of the journal Cancer Research.

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