Gall Tamara M H, Gerrard Gareth, Frampton Adam E, Castellano Leandro, Ahmad Raida, Habib Nagy, Spalding Duncan, Pai Madhava, Foroni Letizia, Jiao Long R
Department of Surgery and Cancer, Imperial College, Hammersmith Hospital Campus, London W12 0HS, United Kingdom.
Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, London W12 0HS, United Kingdom.
Oncotarget. 2019 Jan 22;10(7):696-706. doi: 10.18632/oncotarget.26511.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumour associated with poor 5-year survival. We aimed to determine factors which differentiate short and long-term survivors and identify a prognostic biomarker.
Over a ten-year period, patients with resected PDAC who developed disease recurrence within 12 months (Group I) and those who had no disease recurrence for 24 months (Group II) were identified. Clinicopathological data was analysed. Ion Torrent high-throughput sequencing on DNA extracted from FFPE tumour samples was used to identify mutations. Additionally, peripheral blood samples were analysed for variants in cell-free DNA, circulating tumour cells (CTCs), and microRNAs.
Multivariable analysis of clinicopathological factors showed that a positive medial resection margin was significantly associated with short disease-free survival ( = 0.007). Group I patients ( = 21) had a higher frequency of the mutant mean variant allele (16.93% ± 11.04) compared to those in Group II ( = 13; 7.55% ± 5.76, = 0.0078). Group I patients also trended towards having a c.35G>A p.Gly12Asp mutation in addition to variants in other genes, such as , , and . Mutational status of cell-free DNA, and number of CTCs, was not found to be useful in this study. A circulating miRNA (hsa-miR-548ah-5p) was found to be significantly differentially expressed.
Medial resection margin status and the frequency of mutation in the tumour tissue are independent prognostic indicators for resectable PDAC. Circulating miRNA hsa-miR-548ah-5p has the potential to be used as a prognostic biomarker.
胰腺导管腺癌（PDAC）是一种侵袭性肿瘤，5年生存率较低。我们旨在确定区分短期和长期幸存者的因素，并识别一种预后生物标志物。
在十年期间，确定了切除的PDAC患者，其中12个月内出现疾病复发的患者（第一组）和24个月内无疾病复发的患者（第二组）。分析临床病理数据。对从福尔马林固定石蜡包埋（FFPE）肿瘤样本中提取的DNA进行离子激流高通量测序以识别突变。此外，分析外周血样本中的游离DNA、循环肿瘤细胞（CTC）和微小RNA中的变体。
临床病理因素的多变量分析表明，手术切缘内侧阳性与无病生存期短显著相关（=0.007）。与第二组患者（=13；7.55%±5.76，=0.0078）相比，第一组患者（=21）的KRAS突变平均变异等位基因频率更高（16.93%±11.04）。第一组患者除了其他基因（如NRAS、BRAF和PIK3CA）的变体外，还倾向于有KRAS c.35G>A p.Gly12Asp突变。在本研究中，未发现游离DNA的突变状态和CTC数量有用。发现一种循环微小RNA（hsa-miR-548ah-5p）有显著差异表达。
手术切缘内侧状态和肿瘤组织中KRAS突变频率是可切除PDAC的独立预后指标。循环微小RNA hsa-miR-548ah-5p有潜力用作预后生物标志物。
