Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149, Münster, Germany.
Department of Medicine, Gastroenterology, University Hospital Muenster, Albert-Schweitzer-Campus 1 (A14), 48149, Muenster, Germany.
J Cancer Res Clin Oncol. 2018 Dec;144(12):2377-2390. doi: 10.1007/s00432-018-2749-7. Epub 2018 Sep 17.
Recently, we identified the microRNA-99 family as unfavorable prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to evaluate its value as circulating biomarker for PDAC.
Tissue and corresponding preoperative blood samples of 181 patients with PDAC UICC Stages I-IV (n = 90), intraductal papillary mucinous neoplasm (IPMN, n = 11), chronic pancreatitis (n = 40), pancreatic cystadenoma (n = 20), and age-matched healthy blood serum controls (n = 20) were collected between 2014 and 2017 prospectively. Expression of microRNA-21 as confirmatory marker and the microRNA-99 family, consisting of microRNA-99a, -99b, and -100, was analyzed by qRT-PCR. Target analysis of insulin-like growth factor 1 receptor (IGF1R) was performed using tissue array immunohistochemistry and Western blotting.
Expression of microRNA-99 family members was significantly increased in macrodissected tumor tissue and corresponding blood serum samples (p < 0.05) of patients with PDAC of all stages. Correspondingly, its target protein IGF1R was upregulated (p < 0.001) in carcinoma tissue. Circulating and tissue-related microRNA-100 could well discriminate PDAC from healthy samples with area under the receiver operating characteristic (ROC) curve (AUC) values of 0.81 and 0.85, respectively. Low expression of circulating microRNA-100 was associated with significantly improved overall survival (p = 0.004) and recurrence-free survival (p = 0.03) in multivariate analyses. Circulating microRNA-21 was overexpressed in PDAC with fair discrimination between PDAC and healthy controls (AUC = 0.71) and decreased overall survival (p = 0.046) and recurrence-free survival (p = 0.03) in PDAC patients.
Multivariate survival and ROC analyses identified circulating microRNA-100 as potential diagnostic and prognostic marker in PDAC patients.
最近，我们发现 microRNA-99 家族是胰腺导管腺癌（PDAC）患者不良预后的因素。本研究旨在评估其作为 PDAC 循环生物标志物的价值。
收集了 2014 年至 2017 年期间前瞻性收集的 181 名 PDAC UICC 分期 I-IV 期患者（n=90）、胰管内乳头状黏液性肿瘤（IPMN，n=11）、慢性胰腺炎（n=40）、胰腺囊腺瘤（n=20）和年龄匹配的健康血清对照（n=20）的组织和相应的术前血样。采用 qRT-PCR 分析 microRNA-21 作为确认标志物和 microRNA-99 家族（包括 microRNA-99a、-99b 和 -100）的表达。采用组织 array 免疫组织化学和 Western blot 分析胰岛素样生长因子 1 受体（IGF1R）的靶分析。
在所有分期的 PDAC 患者的大切片肿瘤组织和相应的血清样本中，microRNA-99 家族成员的表达均显著增加（p<0.05）。相应地，其靶蛋白 IGF1R 在癌组织中上调（p<0.001）。循环和组织相关的 microRNA-100 可以很好地区分 PDAC 与健康样本，其接受者操作特征（ROC）曲线下面积（AUC）值分别为 0.81 和 0.85。多变量分析显示，循环 microRNA-100 低表达与总生存率（p=0.004）和无复发生存率（p=0.03）显著提高相关。在 PDAC 患者中，循环 microRNA-21 过度表达，对 PDAC 与健康对照组有较好的区分（AUC=0.71），且总生存率（p=0.046）和无复发生存率（p=0.03）降低。
多变量生存和 ROC 分析确定循环 microRNA-100 是 PDAC 患者潜在的诊断和预后标志物。
