Functional liver genomics identifies hepatokines promoting wasting in cancer cachexia.

In cancer cachexia, the presence of a tumor triggers systemic metabolic disruption that leads to involuntary body weight loss and accelerated mortality in affected patients. Here, we conducted transcriptomic and epigenomic profiling of the liver in various weight-stable cancer and cancer cachexia models. An integrative multilevel analysis approach identified a distinct gene expression signature that included hepatocyte-secreted factors and the circadian clock component REV-ERBα as key modulator of hepatic transcriptional reprogramming in cancer cachexia.

Indirect epigenetic testing identifies a diagnostic signature of cardiomyocyte DNA methylation in heart failure.

Precision-based molecular phenotyping of heart failure must overcome limited access to cardiac tissue. Although epigenetic alterations have been found to underlie pathological cardiac gene dysregulation, the clinical utility of myocardial epigenomics remains narrow owing to limited clinical access to tissue. Therefore, the current study determined whether patient plasma confers indirect phenotypic, transcriptional, and/or epigenetic alterations to ex vivo cardiomyocytes to mirror the failing human myocardium.