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通过加权基因共表达网络分析鉴定与肺腺癌增殖、侵袭和预后相关的 HMGB2。

Identification of HMGB2 associated with proliferation, invasion and prognosis in lung adenocarcinoma via weighted gene co-expression network analysis.

机构信息

Department of Cardiothoracic Surgery, The First People's Hospital of Lianyungang, Lianyungang, People's Republic of China.

Department of Thoracic Surgery, Haian People's Hospital Affiliated to Nantong University, Haian, People's Republic of China.

出版信息

BMC Pulm Med. 2022 Aug 12;22(1):310. doi: 10.1186/s12890-022-02110-y.

Abstract

BACKGROUND

High mobility group protein B2 (HMGB2) is a multifunctional protein that plays various roles in different cellular compartments. Moreover, HMGB2 serves as a potential prognostic biomarker and therapeutic target for lung adenocarcinoma (LUAD).

METHODS

In this study, the expression pattern, prognostic implication, and potential role of HMGB2 in LUAD were evaluated using the integrated bioinformatics analyses based on public available mRNA expression profiles from The Cancer Genome Atlas and Gene Expression Omnibus databases, both at the single-cell level and the tissue level. Further study in the patient-derived samples was conducted to explore the correlation between HMGB2 protein expression levels with tissue specificity, (tumor size-lymph node-metastasis) TNM stage, pathological grade, Ki-67 status, and overall survival. In vitro experiments, such as CCK-8, colony-formation and Transwell assay, were performed with human LUAD cell line A549 to investigate the role of HMGB2 in LUAD progression. Furthermore, xenograft tumor model was generated with A549 in nude mice.

RESULTS

The results showed that the HMGB2 expression was higher in the LUAD samples than in the adjacent normal tissues and was correlated with high degree of malignancy in different public data in this study. Besides, over-expression of HMGB2 promoted A549 cells proliferation and migration while knocking down of HMGB2 suppressed the tumor promoting effect.

CONCLUSIONS

Our study indicated that HMGB2 was remarkably highly expressed in LUAD tissues, suggesting that it is a promising diagnostic and therapeutic marker for LUAD in the future.

摘要

背景

高迁移率族蛋白 B2(HMGB2)是一种多功能蛋白,在不同的细胞区室中发挥多种作用。此外,HMGB2 是肺腺癌(LUAD)的潜在预后生物标志物和治疗靶点。

方法

本研究通过整合公共数据库中基于 TCGA 和 GEO 的 mRNA 表达谱的生物信息学分析,在单细胞水平和组织水平上评估了 HMGB2 在 LUAD 中的表达模式、预后意义和潜在作用。在患者来源的样本中进一步研究,以探索 HMGB2 蛋白表达水平与组织特异性、(肿瘤大小-淋巴结-转移)TNM 分期、病理分级、Ki-67 状态和总生存期之间的相关性。通过 CCK-8、集落形成和 Transwell 测定等体外实验,在人 LUAD 细胞系 A549 中研究了 HMGB2 在 LUAD 进展中的作用。此外,在裸鼠中用 A549 生成了异种移植肿瘤模型。

结果

结果表明,HMGB2 在 LUAD 样本中的表达高于相邻正常组织,并且与本研究中不同公共数据中不同恶性程度相关。此外,HMGB2 的过表达促进了 A549 细胞的增殖和迁移,而 HMGB2 的敲低抑制了肿瘤促进作用。

结论

我们的研究表明,HMGB2 在 LUAD 组织中显著高表达,提示其是未来 LUAD 的有前途的诊断和治疗标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/828f/9373369/b4c8169c5197/12890_2022_2110_Fig1_HTML.jpg

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