微小 RNA-100 和微小 RNA-21 作为 UICC 分期 II 期胰腺导管腺癌生存和化疗反应的标志物。

MicroRNA-100 and microRNA-21 as markers of survival and chemotherapy response in pancreatic ductal adenocarcinoma UICC stage II.

机构信息

Department of General and Visceral Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, Germany.

Department of Pathology, University Hospital Muenster, Albert-Schweitzer-Campus 1 (D17), 48149 Muenster, Germany.

出版信息

Clin Epigenetics. 2015 Dec 23;7:132. doi: 10.1186/s13148-015-0166-1. eCollection 2015.

DOI:10.1186/s13148-015-0166-1

PMID:26705427

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4690288/

Abstract

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) remains a highly chemoresistant tumor entity for which no reliable molecular targets exist to predict or influence the success of chemotherapy. Recently, we identified a panel of microRNAs associated with induced gemcitabine chemoresistance in human PDAC cell lines. This clinical study evaluates these microRNAs and associated molecular markers as prognostic markers of outcome in 98 PDAC patients Union Internationale Contre le Cancer (UICC) stage II undergoing curative surgery with adjuvant gemcitabine chemotherapy. The primary end points of this study are recurrence-free survival and overall survival.

RESULTS

Poor response to chemotherapy was significantly correlated to overexpression of microRNA-21 (p = 0.029), microRNA-99a (p = 0.037), microRNA-100 (p = 0.028), and microRNA-210 (p = 0.021) in tissue samples of PDAC patients UICC stage II. Upregulation of these microRNAs was associated with a significantly shorter overall survival and recurrence-free survival (p < 0.05). Overexpression of phosphatase and tensin homolog (PTEN) (p = 0.039) and low expression of multidrug resistance (MDR)-1 (p = 0.043) and breast cancer resistance protein (BCRP)-1 (p = 0.038) were significantly correlated to improved response to adjuvant chemotherapy. Adjuvant gemcitabine treatment (p < 0.0001) and low tumor grading (p = 0.047) were correlated to better outcome. MicroRNA-100, microRNA-21, and its targets PTEN and MDR-1 were independent factors of survival in multivariate analysis.

CONCLUSIONS

Multivariate survival analyses identified microRNA-21 and microRNA-100 as unfavorable prognostic factors in resected and adjuvant treated PDAC UICC stage II patients.

摘要

背景

胰腺导管腺癌（PDAC）仍然是一种高度耐药的肿瘤实体，目前尚无可靠的分子靶点来预测或影响化疗的疗效。最近，我们发现了一组与人类 PDAC 细胞系中诱导的吉西他滨化疗耐药相关的 microRNAs。本临床研究评估了这些 microRNAs 以及相关的分子标志物，作为 98 名接受联合国际抗癌联盟（UICC）II 期根治性手术和辅助吉西他滨化疗的 PDAC 患者的预后标志物。本研究的主要终点是无复发生存率和总生存率。

结果

化疗反应差与组织样本中 microRNA-21（p=0.029）、microRNA-99a（p=0.037）、microRNA-100（p=0.028）和 microRNA-210（p=0.021）的过度表达显著相关。这些 microRNAs 的上调与总生存率和无复发生存率显著缩短相关（p<0.05）。磷酸酶和张力蛋白同源物（PTEN）的过表达（p=0.039）和多药耐药（MDR）-1（p=0.043）和乳腺癌耐药蛋白（BCRP）-1（p=0.038）的低表达与辅助化疗反应的改善显著相关。辅助吉西他滨治疗（p<0.0001）和低肿瘤分级（p=0.047）与更好的结果相关。多变量分析中，microRNA-100、microRNA-21 及其靶标 PTEN 和 MDR-1 是生存的独立因素。