α-辅肌动蛋白 4 与癌细胞的运动性相关，是一种非小细胞肺癌的潜在生物标志物。

Alpha-actinin 4 is associated with cancer cell motility and is a potential biomarker in non-small cell lung cancer.

机构信息

*Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan. †Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, 100 Shi-Chuan 1st Road, Kaohsiung 807, Taiwan. ‡Translational Research Center, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung 807, Taiwan. §Institute of Medical Science and Technology, National Sun Yat-Sen University, 70 Lienhai Road, Kaohsiung 804, Taiwan. ║Division of Thoracic Surgery, Kaohsing Veterans General Hospital, 386 Ta-Chung 1st RD. Kaohsiung 813, Taiwan. ¶Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan. #Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.

出版信息

J Thorac Oncol. 2015 Feb;10(2):286-301. doi: 10.1097/JTO.0000000000000396.

DOI:10.1097/JTO.0000000000000396

PMID:25299231

Abstract

BACKGROUND

Differential expression and secretion of alpha-actinin 4 (ACTN4) in the lung cancer cell lines CL1-0 and CL1-5 have been reported in previous proteomic studies. The aim of this study is to investigate the functional properties of the ACTN4 protein in non-small-cell lung cancer (NSCLC) cells and evaluate its clinical importance.

METHODS

We used RNA interference to knock down and overexpress ACTN4 protein to evaluate the effects of this intervention on cancer cell invasion and migration, as well as on microscopic cellular morphology. Furthermore, we examined by immunohistochemistry the expression of ACTN4 protein in tissue samples at different stages of lung cancer and compared the protein levels of ACTN4 in blood plasma samples from patients with histologically confirmed lung cancer and healthy controls.

RESULTS

CL1-5 cell motility was significantly suppressed by the knockdown of ACTN4 protein. The morphology of CL1-5 cells changed from a predominantly mesenchymal-like shape into a globular shape in response to ACTN4 protein knockdown. A quantitative immunohistochemical assessment of lung cancer tissues revealed that ACTN4 protein level was considerably higher in cancerous tissues than in the adjacent normal ones, and the area under the receiver operating characteristic curve was 0.736 (p < 0.001). According to an enzyme-linked immunosorbent assay, the plasma levels of ACTN4 protein were significantly different between cancer patients and healthy controls, and the areas under the receiver operating characteristic curves were 0.828 and 0.909, respectively, for two independent cohorts (p < 0.001).

CONCLUSIONS

We demonstrate that the knockdown of ACTN4 protein inhibited cell invasion and migration. These results suggest that ACTN4 is associated with lung cancer cell motility. Thus, the level of ACTN4 in cancerous tissue and plasma is related to the presence of lung cancer.

摘要

背景

在之前的蛋白质组学研究中，已经报道了肺癌细胞系 CL1-0 和 CL1-5 中α-辅肌动蛋白 4（ACTN4）的差异表达和分泌。本研究旨在探讨 ACTN4 蛋白在非小细胞肺癌（NSCLC）细胞中的功能特性，并评估其临床重要性。

方法

我们使用 RNA 干扰敲低和过表达 ACTN4 蛋白，以评估这种干预对癌细胞侵袭和迁移的影响，以及对细胞微观形态的影响。此外，我们通过免疫组织化学检测不同肺癌阶段组织样本中 ACTN4 蛋白的表达，并比较组织学证实的肺癌患者和健康对照者血浆样本中 ACTN4 蛋白的水平。

结果

CL1-5 细胞的运动能力显著受到 ACTN4 蛋白敲低的抑制。CL1-5 细胞的形态从主要的间充质样形状转变为球形，响应于 ACTN4 蛋白敲低。对肺癌组织的定量免疫组织化学评估表明，ACTN4 蛋白水平在癌组织中明显高于相邻正常组织，ROC 曲线下面积为 0.736（p<0.001）。根据酶联免疫吸附试验，癌症患者和健康对照者的 ACTN4 蛋白血浆水平有显著差异，两个独立队列的 ROC 曲线下面积分别为 0.828 和 0.909（p<0.001）。