A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma. Homo sapiens

A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma Pancreatic ductal adenocarcinoma (PDAC), comprising over 90% of all pancreatic cancers, remains a lethal disease with an estimated 232,000 new cases, 227,000 deaths per year worldwide, and a less than 5% five-year survival rate. Currently the standard of care for the 20% of patients with localized disease is surgery followed by chemotherapy, and in some cases radiation. Unfortunately despite the use of adjuvant therapy, median survival remains at best 23 months. It is important to note however, that up to 27% of patients with resected PDAC can survive for five years. However, in these studies examining actual long-term survivors, only two have found that adjuvant therapy was associated with improved survival. In addition, randomized controlled trials of gemcitabine-based chemotherapy demonstrate an improvement in median survival of at best 3 months. One possible conclusion from these studies is that tumor biology dictates outcome and that our current adjuvant therapy has only a modest impact on altering a patient's course.Hypothesizing that the dismal outcome of patients with localized disease is due to the presence of micrometastasic disease, current clinical investigation has focused on preoperative or neoadjuvant therapy. This approach, where patients who cannot tolerate the stress of therapy or develop metastatic disease during treatment are spared surgery, has demonstrated an overall survival of 34 months in this highly selected patient population. Therefore the ability to select patients who would most benefit from a neoadjuvant approach may be important. One way to do this is to define a prognostic gene signature that can identify patients with more aggressive tumor biology upfront. Overall design: reference x sample The 30 Nebraska and UNC samples were not analyzed with clinical data so it is not provided. One of the PE samples is missing some clinical data.

六基因特征可预测局限性胰腺导管腺癌患者的生存结局
胰腺导管腺癌（Pancreatic ductal adenocarcinoma, PDAC）占所有胰腺癌的90%以上，仍是一类致死性疾病。据估计，全球每年新增23.2万例病例、22.7万例死亡，五年生存率不足5%。目前，针对20%表现为局限性病变的患者，标准治疗方案为手术切除后辅以化疗，部分患者还可联合放疗。然而遗憾的是，即便采用辅助治疗，患者的中位生存期最多仅为23个月。但需注意的是，接受根治性切除的PDAC患者中，最高可达27%可存活五年以上。不过在现有针对长期生存者的相关研究中，仅有两项研究证实辅助治疗可改善患者生存结局。此外，以吉西他滨为基础的化疗随机对照试验显示，其最多仅能将中位生存期延长3个月。从上述研究结果可得出一个合理推论：肿瘤生物学特性决定了患者的临床转归，而当前的辅助治疗对改变患者病程的作用十分有限。
研究人员推测，局限性PDAC患者预后极差的原因在于体内存在微转移灶，因此当前的临床研究重点聚焦于术前治疗，即新辅助治疗。该治疗策略会预先筛除无法耐受治疗应激或在治疗期间出现转移性病变的患者，避免其接受手术；在经过严格筛选的患者群体中，该方案已实现34个月的总生存期。因此，筛选出最能从新辅助治疗中获益的患者群体显得尤为关键。实现这一目标的途径之一，便是建立一套预后基因特征，以提前识别出肿瘤生物学特性更具侵袭性的患者。
整体设计：参考样本与样本（reference × sample）
30份取自内布拉斯加大学与UNC的样本未结合临床数据开展分析，故未提供相关临床信息；另有1份PE样本缺失部分临床数据。