An 83-gene signature for cachexia in cancer patients suggests that preclinical models do not accurately reflect the biological processes of this disease in humans, according to research recently published in Genome Medicine.
Cancer cachexia affects up to half of all cancer patients. It causes severe tissue wasting and weight loss which is resistant to increased nutritional intake, and can hasten cancer-related death. The molecular mechanisms behind this disease are poorly understood, and have mostly been examined biochemically or in preclinical models.
In their article “Using transcriptomics to identify and validate novel biomarkers of human skeletal muscle cancer cachexia”, Timmons and colleagues describe RNA profiling of muscle from cancer patients who were defined as either weight-stable or weight-losing since becoming ill. An 83-gene signature for weight loss was determined, which includes many genes not previously associated with this condition in humans or in animal models. The increased expression of genes such as CaMKII and TIE1 may lead to their use as novel molecular biomarkers of human cancer cachexia.
However, some candidates selected from the pre-clinical literature, such as FOXO1, showed no correlation with weight loss in this study. This suggests that some pathways do not play the same role in human cancer cachexia as previously indicated by animal and cell-based studies.
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Assistant Editor, Genome Medicine.