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活化白细胞细胞黏附分子的膜表达有助于非小细胞肺癌的不良预后和恶性表型。

Membranous expression of activated leukocyte cell adhesion molecule contributes to poor prognosis and malignant phenotypes of non-small-cell lung cancer.

机构信息

Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.

出版信息

J Surg Res. 2013 Jan;179(1):24-32. doi: 10.1016/j.jss.2012.08.044. Epub 2012 Sep 7.

DOI:10.1016/j.jss.2012.08.044
PMID:22985775
Abstract

BACKGROUND

Activated leukocyte cell adhesion molecule (ALCAM) has been shown to correlate with the prognosis of patients with various types of human malignancies. However, the relationship between ALCAM expression and progression of non-small-cell lung cancer (NSCLC) has not been investigated. This study was designed to clarify the prognostic impact of ALCAM expression of NSCLC cells.

MATERIALS AND METHODS

The study population consisted of 147 NSCLC patients who underwent complete resection. We performed immunohistochemical staining for ALCAM expression and correlated this to the clinicopathologic parameters and patient survival. The ALCAM expression in NSCLC cell lines was analyzed using quantitative reverse transcription-polymerase chain reaction and Western blot analyses. ALCAM knockdown in NSCLC cell lines was performed with lentivirus-mediated short hairpin RNA transduction.

RESULTS

Positive membranous and cytoplasmic ALCAM expressions were detected in 66 (44.9%) and 57 (38.8%) patients, respectively. A significant association of high membranous ALCAM expression with shortened overall survival (OS) was found (P = 0.009). However, patients with cytoplasmic staining of ALCAM showed no significantly shortened OS (P = 0.723). Multivariate analyses showed that membranous expression was adverse prognostic factors for OS (hazard ratio, 2.11; P = 0.046). ALCAM knockdown with short hairpin RNA suppressed cell migration and invasion of NSCLC cell lines in vitro.

CONCLUSIONS

Strong membranous ALCAM expression is associated with a poor prognosis in patients with resected NSCLC, and overexpression of ALCAM causes malignant phenotypes of NSCLC.

摘要

背景

活化白细胞细胞黏附分子(ALCAM)已被证明与各种人类恶性肿瘤患者的预后相关。然而,ALCAM 表达与非小细胞肺癌(NSCLC)进展之间的关系尚未得到研究。本研究旨在阐明 NSCLC 细胞中 ALCAM 表达的预后影响。

材料与方法

研究人群包括 147 例接受完全切除的 NSCLC 患者。我们对 ALCAM 表达进行了免疫组织化学染色,并将其与临床病理参数和患者生存相关联。使用定量逆转录-聚合酶链反应和 Western blot 分析来分析 NSCLC 细胞系中的 ALCAM 表达。使用慢病毒介导的短发夹 RNA 转导来进行 NSCLC 细胞系中的 ALCAM 敲低。

结果

在 66 例(44.9%)和 57 例(38.8%)患者中分别检测到阳性的膜和细胞质 ALCAM 表达。高膜 ALCAM 表达与总生存期(OS)缩短显著相关(P = 0.009)。然而,细胞质染色的 ALCAM 患者的 OS 没有明显缩短(P = 0.723)。多变量分析表明,膜表达是 OS 的不良预后因素(风险比,2.11;P = 0.046)。用短发夹 RNA 进行的 ALCAM 敲低抑制了 NSCLC 细胞系在体外的迁移和侵袭。

结论

强烈的膜 ALCAM 表达与接受 NSCLC 切除的患者的不良预后相关,并且 ALCAM 的过表达导致 NSCLC 的恶性表型。

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