Vietsch Eveline E, Peran Ivana, Suker Mustafa, van den Bosch Thierry P P, van der Sijde Fleur, Kros Johan M, van Eijck Casper H J, Wellstein Anton
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA.
Department of Surgery, Erasmus MC, University Medical Center Rotterdam, 3015GD Rotterdam, The Netherlands.
Appl Sci (Basel). 2019 Nov 2;9(22). doi: 10.3390/app9224784. Epub 2019 Nov 8.
Clinical follow-up aided by changes in the expression of circulating microRNAs (miRs) may improve prognostication of pancreatic ductal adenocarcinoma (PDAC) patients. Changes in 179 circulating miRs due to cancer progression in the transgenic ; ; (KPC) animal model of PDAC were analyzed for serum miRs that are altered in metastatic disease. In addition, expression levels of 250 miRs were profiled before and after pancreaticoduodenectomy in the serum of two patients with resectable PDAC with different progression free survival (PFS) and analyzed for changes indicative of PDAC recurrence after resection. Three miRs that were upregulated ≥3-fold in progressive PDAC in both mice and patients were selected for validation in 26 additional PDAC patients before and after resection. We found that high serum miR-125b-5p and miR-99a-5p levels after resection are significantly associated with shorter PFS (HR 1.34 and HR 1.73 respectively). In situ hybridization for miR detection in the paired resected human PDAC tissues showed that miR-125b-5p and miR-99a-5p are highly expressed in inflammatory cells in the tumor stroma, located in clusters of CD79A expressing cells of the B-lymphocyte lineage. In conclusion, we found that circulating miR-125b-5p and miR-99a-5p are potential immune-cell related prognostic biomarkers in PDAC patients after surgery.
循环微小RNA（miR）表达变化辅助的临床随访可能改善胰腺导管腺癌（PDAC）患者的预后。分析了转基因KPC PDAC动物模型中由于癌症进展导致的179种循环miR的变化，以寻找在转移性疾病中发生改变的血清miR。此外，对两名具有不同无进展生存期（PFS）的可切除PDAC患者血清在胰十二指肠切除术前和术后的250种miR表达水平进行了分析，并分析了提示切除术后PDAC复发的变化。选择在小鼠和患者的进展性PDAC中上调≥3倍的三种miR在另外26名PDAC患者切除术前和术后进行验证。我们发现，切除术后血清miR-125b-5p和miR-99a-5p水平升高与较短的PFS显著相关（HR分别为1.34和1.73）。在配对的切除的人PDAC组织中进行miR检测的原位杂交显示，miR-125b-5p和miR-99a-5p在肿瘤基质中的炎症细胞中高表达，这些炎症细胞位于B淋巴细胞谱系的表达CD79A的细胞簇中。总之，我们发现循环miR-125b-5p和miR-99a-5p是PDAC患者术后潜在的免疫细胞相关预后生物标志物。
