Skeletal Muscle Fibrosis in Pancreatic Cancer Patients with Respect to Survival

Skeletal muscle wasting is a devastating consequence of cancer that may be responsible for nearly 30% of cancer-related deaths. In addition to muscle atrophy, we have identified significant muscle fiber damage and replacement of muscle with fibrotic tissue in rectus abdominis muscle biopsies from cachectic pancreatic ductal adenocarcinoma (PDAC) patients that associates with poor survival. Transcriptional profiling of muscle harvested from these same patients supported these findings by identifying gene clusters related to wounding, inflammation and cellular response to TGF-B upregulated in cachectic PDAC patients compared with non-cancer controls. In this dataset, we include the expression data obtained from rectus abdominis muscle biopsies fron non-cancer controls patients undergoing abdominal surgery for benign reasons and from PDAC patients undergoing tumor-resection surgery. PDAC patients were further classified as non-cachectic or cachectic. Cachexia was defined as a body weight loss of >5% during the 6 months prior to surgery. The purpose of this study was to identify the broader transcriptional networks changed in cachectic PDAC patients versus non-cancer controls, that may be associated with the histological changes observed in muscle biopsies harvested from these same patients. For microarray analysis, a total of 46 RNA samples across four groups are included. The groups are as follows: Non-cancer control patients (n = 16); Chronic pancreatitis patients (n = 8); Non-cachectic PDAC patients (n = 5); Cachectic PDAC patients (n = 17). To identify broader gene networks changed in cachectic PDAC patients that may be associated with histological findings of muscle damage and replacement of muscle with fat and fibrotic tissue, we performed differential expression analysis between non-cancer controls and cachectic PDAC patients, and between non-cancer controls and non-cachectic PDAC patients. PDAC patients receiving Stage IV diagnosis were excluded from analyses. Due to the inflammatory nature of chronic pancreatitis, patients diagnosed with chronic pancreatitis were not included in the non-cancer control group and were excluded from analyses.