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鉴定 AUNIP 为口腔鳞状细胞癌的候选诊断和预后生物标志物。

Identification of AUNIP as a candidate diagnostic and prognostic biomarker for oral squamous cell carcinoma.

机构信息

School of Stomatology, Shandong University, Jinan, Shandong 250012, PR China; Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Shandong 250012, PR China.

Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of BasicMedical Science, Shandong University, Jinan, Shandong 250012, PR China; Shandong University, Karolinska Institutet Collaborative Laboratory for Cancer Research, Jinan, Shandong 250012, PR China.

出版信息

EBioMedicine. 2019 Sep;47:44-57. doi: 10.1016/j.ebiom.2019.08.013. Epub 2019 Aug 10.

DOI:10.1016/j.ebiom.2019.08.013
PMID:31409573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6796785/
Abstract

BACKGROUND

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors worldwide. Patients with poorly differentiated OSCC often exhibit a poor prognosis. AUNIP (Aurora Kinase A and Ninein Interacting Protein), also known as AIBp, plays a key role in cell cycle and DNA damage repair. However, the function of AUNIP in OSCC remains elusive.

METHODS

The differentially expressed genes (DEGs) were obtained using R language. Receiver operating characteristic curve analysis was performed to identify diagnostic markers for OSCC. The effectiveness of AUNIP in diagnosing OSCC was evaluated by machine learning. AUNIP expression was analyzed in publicly available databases and clinical specimens. Bioinformatics analysis and in vitro experiments were conducted to explore biological functions and prognostic value of AUNIP in OSCC.

FINDINGS

The gene integration analysis revealed 90 upregulated DEGs. One candidate biomarker, AUNIP, for the diagnosis of OSCC was detected, and its expression gradually increased along with malignant differentiation of OSCC. Bioinformatics analysis demonstrated that AUNIP could be associated with tumor microenvironment, human papillomavirus infection, and cell cycle in OSCC. The suppression of AUNIP inhibited OSCC cell proliferation and resulted in G0/G1 phase arrest in OSCC cells. The survival analysis showed that AUNIP overexpression predicted poor prognosis of OSCC patients.

INTERPRETATION

AUNIP could serve as a candidate diagnostic and prognostic biomarker for OSCC and suppression of AUNIP may be a potential approach to preventing and treating OSCC. FUND: Taishan Scholars Project in Shandong Province (ts201511106) and the National Natural Science Foundation of China (Nos. 61603218).

摘要

背景

口腔鳞状细胞癌(OSCC)是全球最常见的恶性肿瘤之一。低分化 OSCC 患者常预后不良。AUNIP(极光激酶 A 和 Ninein 相互作用蛋白)又称为 AIBp,在细胞周期和 DNA 损伤修复中发挥关键作用。然而,AUNIP 在 OSCC 中的功能仍不清楚。

方法

使用 R 语言获取差异表达基因(DEGs)。通过接受者操作特征曲线分析,鉴定 OSCC 的诊断标志物。通过机器学习评估 AUNIP 诊断 OSCC 的有效性。在公开可用的数据库和临床标本中分析 AUNIP 表达。通过生物信息学分析和体外实验,探讨 AUNIP 在 OSCC 中的生物学功能和预后价值。

发现

基因整合分析显示 90 个上调的 DEGs。发现一个用于 OSCC 诊断的候选生物标志物 AUNIP,其表达随着 OSCC 恶性分化程度逐渐增加。生物信息学分析表明,AUNIP 可能与 OSCC 中的肿瘤微环境、人乳头瘤病毒感染和细胞周期有关。抑制 AUNIP 抑制 OSCC 细胞增殖并导致 OSCC 细胞 G0/G1 期停滞。生存分析表明 AUNIP 过表达预示 OSCC 患者预后不良。

结论

AUNIP 可作为 OSCC 的候选诊断和预后生物标志物,抑制 AUNIP 可能是预防和治疗 OSCC 的一种潜在方法。

资助

山东省泰山学者工程(ts201511106)和国家自然科学基金(Nos. 61603218)。

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