Date of Award
Doctor of Philosophy (Medical Science)
Thomas E. Adrian
Cancer cachexia is responsible for one third of cancer–related deaths and contributes to the death of many others. More than 80% of cancer patients are cachectic towards the end of life. Despite intensive research, the mechanisms of cancer cachexia are still poorly understood. It is our hypothesis that identification of early changes in gene expression in cachexia will lead to an improved understanding of the mechanism that trigger this important problem in cancer patients. Thus, to shed light on the mechanisms involved in the major cachexia target tissues, we investigated the entire transcriptome in muscle and fat to identify altered expression of genes in cancer patients with and without cachexia. Samples of rectus abdominis muscle and visceral fat were collected at surgery from patients exhibiting 5-10% weight loss prior to surgery, compared with stable-weight patients. Analysis of all expressed genes was carried out using next generation sequencing (Illumina HiSeq 2500). Also, selected differentially expressed genes were confirmed using real time RT-PCR. In muscle, 30 genes showed highly significant changes in expression (25 downregulated and 5 upregulated: P
In visceral fat, expression of 6 genes were downregulated and 10 upregulated with high statistical significance (P
Al Hadad, Amal Hussain, "IDENTIFYING THE MOLECULAR MECHANISMS OF EARLY CACHEXIA USING WHOLE TRANSCRIPTOME SEQUENCING IN MUSCLE AND FAT BIOPSIES FROM CANCER PATIENTS" (2015). Dissertations. 5.