Skeletal Muscle Fibrosis in Pancreatic Cancer Patients with Respect to Survival. 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. Overall design: 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.

骨骼肌消耗是癌症的一种严重并发症，其可能导致近30%的癌症相关死亡。除肌肉萎缩外，我们在恶病质型胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）患者的腹直肌活检标本中观察到显著的肌纤维损伤以及肌肉被纤维化组织替代的现象，且该现象与患者不良预后相关。对同一批患者的肌肉组织进行转录组谱分析后，我们鉴定出与创伤应答、炎症以及转化生长因子β（TGF-β）细胞应答相关的基因簇在恶病质型PDAC患者中较非癌症对照组显著上调，验证了前述发现。本数据集包含来自两类受试者的腹直肌活检标本的表达谱数据：一类为因良性疾病接受腹部手术的非癌症对照受试者，另一类为接受肿瘤切除术的PDAC患者。PDAC患者进一步分为非恶病质组与恶病质组，其中恶病质的定义为术前6个月内体重下降超过5%。本研究旨在鉴定与非癌症对照受试者相比，恶病质型PDAC患者中发生改变的更广泛转录调控网络，这些网络可能与从同一批受试者获取的肌肉活检标本中观察到的组织病理学改变相关。总体实验设计：本研究的微阵列分析共纳入4组共46份RNA样本，分组情况如下：非癌症对照组受试者（n=16）、慢性胰腺炎患者（n=8）、非恶病质型PDAC患者（n=5）以及恶病质型PDAC患者（n=17）。为鉴定恶病质型PDAC患者中与肌肉损伤及肌肉被脂肪与纤维化组织替代的组织病理学改变相关的更广泛基因网络，我们分别开展了非癌症对照组与恶病质型PDAC患者之间、非癌症对照组与非恶病质型PDAC患者之间的差异表达分析。确诊为IV期的PDAC患者被排除出本分析。由于慢性胰腺炎具有炎症特性，确诊为慢性胰腺炎的患者未被纳入非癌症对照组，同时也被排除出本分析。