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Loss of ARID1A expression promotes lung adenocarcinoma metastasis and predicts a poor prognosis
Cellular Oncology ( IF 6.6 ) Pub Date : 2021-06-09 , DOI: 10.1007/s13402-021-00616-x
Dantong Sun 1 , Yan Zhu 2 , Han Zhao 3 , Tiantian Bian 4 , Tianjun Li 1 , Kewei Liu 1 , Lizong Feng 5 , Hong Li 6 , Helei Hou 1
Affiliation  

Background

ARID1A is an essential subunit of SWI/SNF chromatin remodeling complexes. ARID1A gene mutations and loss of ARID1A expression have been observed in a variety of cancers, and to be correlated with invasion, immune escape and synthetic lethality. As yet, however, the biological effect of ARID1A expression and its role in the prognosis of lung adenocarcinoma (LUAD) patients have remained unclear. In this study we aimed to further elucidate the role of ARID1A expression in LUAD in vitro and in vivo and to assess its effect on the clinical prognosis of LUAD patients.

Methods

ARID1A expression was detected by IHC in tissue samples from LUAD patients. After regular culturing of LUAD cell lines and constructing stable ARID1A knockdown lines, wound healing and Transwell assays were used to assess the role of ARID1A in cell migration and invasion. The effect of ARID1A knockdown on metastasis was verified in vivo. Western blotting was used to examine the expression of target proteins. Univariate and multivariate analyses were performed to assess survival and to provide variables for nomogram construction. In addition, we used the “rms” package to construct a prognostic nomogram based on a Cox regression model.

Results

We found that ARID1A expression serves as an effective prognostic marker for LUAD patients. Loss of ARID1A expression correlated with a poor prognosis, as verified with a nomogram based on a Cox regression model. In addition, we found that ARID1A knockdown promoted LUAD cell proliferation, migration and invasion in vitro and enhanced LUAD metastasis in vivo by activating the Akt signaling pathway.

Conclusions

Our data indicate that loss of ARID1A expression promotes LUAD metastasis and predicts a poor prognosis in LUAD patients.



中文翻译:

ARID1A 表达缺失促进肺腺癌转移并预测不良预后

背景

ARID1A 是 SWI/SNF 染色质重塑复合物的重要亚基。已在多种癌症中观察到ARID1A基因突变和 ARID1A 表达缺失,并与侵袭、免疫逃逸和合成致死率相关。然而,迄今为止,ARID1A 表达的生物学效应及其在肺腺癌 (LUAD) 患者预后中的作用仍不清楚。在这项研究中,我们旨在进一步阐明 ARID1A 表达在体外体内LUAD 中的作用,并评估其对 LUAD 患者临床预后的影响。

方法

通过 IHC 在 LUAD 患者的组织样本中检测到 ARID1A 的表达。在定期培养 LUAD 细胞系并构建稳定的 ARID1A 敲低系后,使用伤口愈合和 Transwell 测定来评估 ARID1A 在细胞迁移和侵袭中的作用。在体内验证了 ARID1A 敲低对转移的影响。Western印迹用于检查靶蛋白的表达。进行单变量和多变量分析以评估生存率并为列线图构建提供变量。此外,我们使用“rms”包来构建基于 Cox 回归模型的预后列线图。

结果

我们发现 ARID1A 表达可作为 LUAD 患者的有效预后标志物。ARID1A 表达的缺失与预后不良相关,如基于 Cox 回归模型的列线图所证实的。此外,我们发现 ARID1A 敲低在体外促进 LUAD 细胞增殖、迁移和侵袭,并通过激活 Akt 信号通路增强 LUAD体内转移。

结论

我们的数据表明,ARID1A 表达的缺失会促进 LUAD 转移并预测 LUAD 患者的不良预后。

更新日期:2021-06-10
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