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整合素 α7 高表达与肿瘤恶化特征相关,与更差的总生存期相关,其敲低可抑制乳腺癌细胞增殖和侵袭,但增加细胞凋亡。

Integrin α7 high expression correlates with deteriorative tumor features and worse overall survival, and its knockdown inhibits cell proliferation and invasion but increases apoptosis in breast cancer.

机构信息

Department of Breast Surgery, GanSu Provincial Cancer Hospital, Lanzhou, China.

Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

出版信息

J Clin Lab Anal. 2019 Oct;33(8):e22979. doi: 10.1002/jcla.22979. Epub 2019 Jul 19.

Abstract

BACKGROUND

This study aimed to investigate the correlation of integrin α7 (ITGA7) expression with clinical/pathological characteristics and overall survival (OS), and its knockdown on inhibiting cell activities in breast cancer.

METHODS

A total of 191 breast cancer patients underwent surgery were retrospectively reviewed, and ITGA7 expression in tumor tissues was determined by immunofluorescence and real-time quantitative polymerase chain reaction. Patients' clinical/pathological data were recorded, and OS was calculated. In vitro, control shRNA and ITGA7 shRNA plasmids were transfected into MCF7 cells to evaluate the influence of ITGA7 knockdown on cell proliferation, apoptosis, and invasion.

RESULTS

Ninety-two (48.2%) patients presented with ITGA7 high expression, and 99 patients (51.8%) presented with ITGA7 low expression. ITGA7 expression was positively correlated with T stage, tumor-node metastasis (TNM) stage, and pathological grade. Kaplan-Meier curves showed that ITGA7 high expression was associated with shorter OS, and multivariate Cox's proportional hazards regression displayed that ITGA7 high expression was an independent predictive factor for poor OS. Moreover, in vitro experiments disclosed that cell proliferation (by Cell Counting Kit-8 assay) and cell invasion (by Matrigel invasion assay) were reduced, while cell apoptosis rate (by Annexin V/propidium iodide assay) was enhanced by ITGA7 knockdown in MCF-7 cells.

CONCLUSION

Integrin α7 high expression correlates with increased T stage, TNM stage, and pathological grade as well as worse OS, and its knockdown enhances cell apoptosis but inhibits cell proliferation and invasion in breast cancer.

摘要

背景

本研究旨在探讨整合素 α7(ITGA7)表达与临床/病理特征和总生存期(OS)的相关性,以及其敲低对乳腺癌细胞活性的抑制作用。

方法

回顾性分析 191 例接受手术治疗的乳腺癌患者,采用免疫荧光和实时定量聚合酶链反应检测肿瘤组织中 ITGA7 的表达。记录患者的临床/病理数据并计算 OS。体外将对照 shRNA 和 ITGA7 shRNA 质粒转染 MCF7 细胞,评估 ITGA7 敲低对细胞增殖、凋亡和侵袭的影响。

结果

92 例(48.2%)患者 ITGA7 高表达,99 例(51.8%)患者 ITGA7 低表达。ITGA7 表达与 T 分期、肿瘤-淋巴结-转移(TNM)分期和病理分级呈正相关。Kaplan-Meier 曲线显示,ITGA7 高表达与 OS 较短相关,多因素 Cox 比例风险回归显示 ITGA7 高表达是 OS 不良的独立预测因素。此外,体外实验表明,ITGA7 敲低可降低 MCF-7 细胞的细胞增殖(通过细胞计数试剂盒-8 检测)和细胞侵袭(通过 Matrigel 侵袭检测),而增加细胞凋亡率(通过 Annexin V/碘化丙啶检测)。

结论

整合素 α7 高表达与 T 分期、TNM 分期和病理分级增加以及 OS 较差相关,其敲低可增强乳腺癌细胞凋亡,抑制细胞增殖和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dd1/6805256/dabd8eb02df9/JCLA-33-e22979-g001.jpg

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