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头颈部鳞状细胞癌风险中干性相关基因的鉴定

The Identification of Stemness-Related Genes in the Risk of Head and Neck Squamous Cell Carcinoma.

作者信息

Feng Guanying, Xue Feifei, He Yingzheng, Wang Tianxiao, Yuan Hua

机构信息

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.

出版信息

Front Oncol. 2021 Jun 11;11:688545. doi: 10.3389/fonc.2021.688545. eCollection 2021.

Abstract

OBJECTIVES

This study aimed to identify genes regulating cancer stemness of head and neck squamous cell carcinoma (HNSCC) and evaluate the ability of these genes to predict clinical outcomes.

MATERIALS AND METHODS

The stemness index (mRNAsi) was obtained using a one-class logistic regression machine learning algorithm based on sequencing data of HNSCC patients. Stemness-related genes were identified by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis (LASSO). The coefficient of LASSO was applied to construct a diagnostic risk score model. The Cancer Genome Atlas database, the Gene Expression Omnibus database, Oncomine database and the Human Protein Atlas database were used to validate the expression of key genes. Interaction network analysis was performed using String database and DisNor database. The Connectivity Map database was used to screen potential compounds. The expressions of stemness-related genes were validated using quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

TTK, KIF14, KIF18A and DLGAP5 were identified. Stemness-related genes were upregulated in HNSCC samples. The risk score model had a significant predictive ability. CDK inhibitor was the top hit of potential compounds.

CONCLUSION

Stemness-related gene expression profiles may be a potential biomarker for HNSCC.

摘要

目的

本研究旨在鉴定调节头颈部鳞状细胞癌(HNSCC)癌干性的基因,并评估这些基因预测临床结局的能力。

材料与方法

基于HNSCC患者的测序数据,使用单类逻辑回归机器学习算法获得干性指数(mRNAsi)。通过加权基因共表达网络分析和最小绝对收缩和选择算子分析(LASSO)鉴定干性相关基因。应用LASSO系数构建诊断风险评分模型。使用癌症基因组图谱数据库、基因表达综合数据库、Oncomine数据库和人类蛋白质图谱数据库验证关键基因的表达。使用String数据库和DisNor数据库进行相互作用网络分析。使用连通性图谱数据库筛选潜在化合物。使用定量实时聚合酶链反应(qRT-PCR)验证干性相关基因的表达。

结果

鉴定出TTK、KIF14、KIF18A和DLGAP5。干性相关基因在HNSCC样本中上调。风险评分模型具有显著的预测能力。CDK抑制剂是潜在化合物的首要靶点。

结论

干性相关基因表达谱可能是HNSCC的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af96/8226229/b6b2f2ca621d/fonc-11-688545-g001.jpg

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