m6a相关基因ALKBH5和RBMX作为中国口腔鳞状细胞癌患者预后和进展的生物标志物

IF 2.2 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology Pub Date : 2025-02-01 DOI:10.1016/j.archoralbio.2024.106149

Yong Liu , Jiaying Nie , Ying Huang , Yunyan Yang , Wenen Su , Yumei Zhang , Zhuoqiao Gao , Shaohui Deng , Meilin Li , Shaoyan Lian , Jieying Li , Chaoqun Liu

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引用次数: 0

摘要

目的：n6 -甲基腺苷（n6 - methylladenosine, m6A） RNA异常在肿瘤发生发展中起着至关重要的作用。本研究旨在探讨m6A修饰在口腔鳞状细胞癌（OSCC）中的作用及其作为生物标志物和治疗靶点的潜力。设计：我们首先使用TCGA数据库分析m6a相关基因表达及其对OSCC预后和进展的影响。随后，使用中国134个样本队列进行验证。使用TCGA数据进行生物信息学分析，并使用定量试剂盒测量验证队列中的m6A水平。通过生存分析研究中国人群中m6a相关基因与OSCC预后的关系。采用实时荧光定量PCR、Western blot和免疫组织化学检测m6a相关基因的表达。结果：在TCGA数据库中，我们发现metttl14、ALKBH5、YTHDF2、HNRNPC、LRPPRC、HNRNPA2B1、IGF2BP2、RBMX在OSCC中表达异常。基于此，我们观察到在验证队列中，与正常对照相比，OSCC组织中总m6A含量显著升高。在m6A候选基因中，只有ALKBH5和RBMX上调被发现是中国人群OSCC生存不良的独立预后危险因素。与仅考虑临床参数的模型相比，纳入这两个基因的3年（0.705,0.826）和5年（0.715,0.788）总生存率曲线下面积更高。结论：我们发现在OSCC中m6A水平上调，其中ALKBH5和RBMX可能作为中国OSCC患者有希望的诊断和预后生物标志物。

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m6A-related genes ALKBH5 and RBMX as prognostic and progression biomarkers in Chinese oral squamous cell carcinoma patients

Objective

N6-methyladenosine (m6A) RNA dysregulation is crucial for cancer development. The study aimed to explore the effects of m6A modification in oral squamous cell carcinoma (OSCC) and its potential as a biomarker and therapeutic target.

Design

We first analyzed m6A-related gene expression and its impact on OSCC prognosis and progression using the TCGA database. Subsequently, a Chinese cohort of 134 samples was used for validation. Bioinformatics analysis was conducted with TCGA data, and m6A levels were measured in the validation cohort using a quantification kit. Survival analysis was performed to study the relationship between m6A-related genes and OSCC prognosis in the Chinese population. The expression of m6A-related genes was assessed by using quantitative real-time PCR, Western blot analysis, and immunohistochemistry.

Results

In the TCGA database, we found dysregulated expressions of METTL14, ALKBH5, YTHDF2, HNRNPC, LRPPRC, HNRNPA2B1, IGF2BP2, and RBMX in OSCC. Based on this, we observed significantly elevated total m6A content in OSCC tissues compared to normal controls in the validation cohort. Among the m6A candidate genes, only ALKBH5 and RBMX upregulation were found to be independent prognostic risk factors for poor OSCC survival in the Chinese population. And the inclusion of these two genes had a higher area under the curve for 3-year (0.705, 0.826), and 5-year (0.715, 0.788) overall survival compared to the model that only considered clinical parameters.

Conclusions

We found the upregulation of m6A status in OSCC, of which, ALKBH5 and RBMX may serve as promising diagnostic and prognostic biomarkers for Chinese patients with OSCC.

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来源期刊

Archives of oral biology 医学-牙科与口腔外科

CiteScore

5.10

自引率

3.30%

发文量

177

审稿时长

26 days

期刊介绍： Archives of Oral Biology is an international journal which aims to publish papers of the highest scientific quality in the oral and craniofacial sciences. The journal is particularly interested in research which advances knowledge in the mechanisms of craniofacial development and disease, including: Cell and molecular biology Molecular genetics Immunology Pathogenesis Cellular microbiology Embryology Syndromology Forensic dentistry