oa RNA -seq Study Of Muscle And Adipose Tissue In Cancer Patients With Early Cachexia

Objectives: Cancer cachexia is a syndrome characterized by weight loss resulting from a reduction of lean body mass and adipose mass. Although often associated with pre-terminal patients bearing disseminated disease, cachexia may be present in the early stages of tumor growth before any signs or symptoms of malignancy. Studies show that weight loss in cachexia is not caused by malnutrition or starvation but, rather, by inflammatory changes associated with the presence of the tumor and the production of cytokines. The purpose of this study is to investigate gene expression changes in muscle-adipose wasting and cachexia. Methods: RNA was extracted from 6 muscle and 6 adipose human tissue samples from 6 patients with cancer cachexia. 6 muscle and 6 adipose tissue samples from 12 controls were also collected. RNA-seq was performed on the samples to identify both genes and pathways that are affected by cachexia. Comparisons were made between muscle and adipose of cachectic and control patients. Results: Analysis of the RNA-seq data showed that 4 pathways are especially up regulated in cachectic muscle samples (Notch signaling pathway, Cell adhesion molecules..) and 11 pathways are down regulated (Hypertrophic cardiomyopathy, Insulin signaling pathway..). While in cachectic adipose samples, there are 5 pathways up regulated (Cytokine-cytokine receptor interaction, N-Glycan biosynthesis…) and only one pathway is down regulated (Neuroactive ligand-receptor interaction). Muscle samples were more clearly affected at the gene expression level than were adipose samples. Conclusion: For the first time we have identified consistent gene expression changes in cancer patients experiencing cachexia. These changes should lead to development of markers for early diagnosis and a better understanding of the conditions that lead to cachexia.