Arpin 下调与胰腺导管腺癌不良预后相关。

Arpin downregulation is associated with poor prognosis in pancreatic ductal adenocarcinoma.

机构信息

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 20032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, PR China.

出版信息

Eur J Surg Oncol. 2019 May;45(5):769-775. doi: 10.1016/j.ejso.2018.10.539. Epub 2018 Oct 30.

DOI:10.1016/j.ejso.2018.10.539

PMID:30416079

Abstract

INTRODUCTION

Arpin (Arp2/3 complex inhibitor), a novel protein found in 2013, plays a pivotal role in cell motility and migration. However, the prognostic value of Arpin in pancreatic ductal adenocarcinoma (PDAC) remains unknown.

MATERIALS AND METHODS

We analyzed the gene expression of ARPIN using the GEO dataset (GSE71989) and validated the results by immunohistochemistry (IHC) and Western blot in our clinical database. Tissue microarray specimens from 214 patients who underwent curative pancreatectomy for PDAC were used. The tumors that expressed high and low levels of Arpin were compared with patient outcome using Kaplan-Meier curves and the multivariate Cox proportional hazard regression model. IHC was then used in 43 paired primary tumor tissues and metastasis tissues to detect the expression of Arpin.

RESULTS

Arpin had low expression in the tumor tissue compared with the paracancerous tissue in PDAC. Patients with low intratumoral Arpin expression had worse overall survival (OS) and recurrence-free survival (RFS) than patients with high expression in the training set (p < 0.001, p < 0.001) and validation set (p < 0.001, p < 0.001). The multivariate analysis revealed that the 8th edition TNM stage and Arpin expression were independent prognostic factors associated with OS and RFS in the training and validation sets, respectively. Arpin had lower expression in the metastasis tissues than in the primary tumors of patients with PDAC (p = 0.048).

CONCLUSION

The Arpin level is an independent prognostic factor that can be a potential predictor to aid in the management of PDAC.

摘要

简介

Arpin（Arp2/3 复合物抑制剂）是一种于 2013 年发现的新型蛋白，在细胞运动和迁移中发挥着关键作用。然而，Arpin 在胰腺导管腺癌（PDAC）中的预后价值尚不清楚。

材料与方法

我们使用 GEO 数据集（GSE71989）分析 ARPIN 的基因表达，并通过免疫组织化学（IHC）和 Western blot 在我们的临床数据库中验证结果。使用了 214 名接受根治性胰切除术治疗 PDAC 的患者的组织微阵列标本。通过 Kaplan-Meier 曲线和多变量 Cox 比例风险回归模型，比较表达高、低水平 Arpin 的肿瘤与患者结局。然后使用 IHC 在 43 对原发肿瘤组织和转移组织中检测 Arpin 的表达。

结果

与 PDAC 中的癌旁组织相比，Arpin 在肿瘤组织中的表达较低。在训练集（p<0.001，p<0.001）和验证集（p<0.001，p<0.001）中，低肿瘤内 Arpin 表达的患者总生存期（OS）和无复发生存期（RFS）均较高表达的患者差。多变量分析显示，第 8 版 TNM 分期和 Arpin 表达是与训练集和验证集 OS 和 RFS 相关的独立预后因素。在 PDAC 患者中，转移组织中的 Arpin 表达低于原发肿瘤（p=0.048）。