Identification of novel biomarkers involved in oral squamous cell carcinoma by whole transcriptome sequencing and bioinformatics analysis.

IF 6 2区 医学 Q1 ONCOLOGY
Hongliang Du, Zhenze Wang, Mengyi Qi, Yunqing Pang, Qingling Lin, Dengqi He, Jing Wang
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引用次数: 0

Abstract

Background: Oral squamous cell carcinoma (OSCC) is among the most common malignant tumors in the oral and maxillofacial regions, characterized by high drug resistance and poor treatment outcomes. This underscores the urgent need to identify novel biomarkers for OSCC.

Methods: Differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) (DE-mRNAs, DE-miRNAs, and DE-lncRNAs) between primary and control groups, as well as metastatic and primary groups, were identified using whole transcriptome sequencing data. Candidate OSCC genes were derived from DE-mRNAs. Potential biomarkers were then identified using five algorithms from CytoHubba. Biomarkers were validated via univariate Cox regression and Kaplan-Meier (K-M) survival analysis. Additional analyses included subcellular localization, mutation analysis, and Gene Set Enrichment Analysis (GSEA). Key drugs for OSCC treatment were also identified. Quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry were employed to verify the expression levels of key biomarkers.

Results: A total of 304 candidate genes were identified, with 29 potential biomarkers selected by five algorithms. ANPEP, APOB, GLP1R, and SI exhibited significant survival differences in the K-M curves, establishing them as OSCC biomarkers. These biomarkers were predominantly localized in the cytoplasm, with SI and APOB showing the highest mutation susceptibility. Enrichment analysis revealed that the 'interferon-gamma response'biological function was co-enriched by ANPEP, APOB, and SI. Furthermore, BIBW2992 (afatinib) and PF.02341066 (crizotinib) were most strongly correlated with the biomarkers, suggesting their potential as key drugs for OSCC treatment. Additionally, the findings were validated by qRT-PCR and immunohistochemical analyses, and the results were consistent with the RNA-seq data.

Conclusion: ANPEP, APOB, GLP1R, and SI were identified as potential OSCC biomarkers, offering valuable insights for further research and therapeutic development.

利用全转录组测序和生物信息学分析鉴定与口腔鳞状细胞癌相关的新生物标志物。
背景:口腔鳞状细胞癌(Oral squamous cell carcinoma, OSCC)是口腔颌面部最常见的恶性肿瘤之一,耐药高,治疗效果差。这强调了迫切需要确定新的OSCC生物标志物。方法:利用全转录组测序数据,鉴定原发性组和对照组以及转移性组和原发性组之间差异表达的信使rna (mrna)、微小rna (miRNAs)和长链非编码rna (lncRNAs) (de - mrna、DE-miRNAs和DE-lncRNAs)。候选OSCC基因来源于de - mrna。然后使用CytoHubba的五种算法鉴定潜在的生物标志物。生物标志物通过单变量Cox回归和Kaplan-Meier (K-M)生存分析进行验证。其他分析包括亚细胞定位、突变分析和基因集富集分析(GSEA)。同时确定了治疗OSCC的关键药物。采用定量实时聚合酶链反应(qRT-PCR)和免疫组织化学方法验证关键生物标志物的表达水平。结果:共鉴定出304个候选基因,通过5种算法筛选出29个潜在的生物标志物。ANPEP、APOB、GLP1R和SI在K-M曲线上表现出显著的生存差异,可以作为OSCC的生物标志物。这些生物标志物主要定位于细胞质中,其中SI和APOB表现出最高的突变易感性。富集分析显示,ANPEP、APOB和SI共同富集了“干扰素- γ反应”生物学功能。此外,BIBW2992(阿法替尼)和pff .02341066(克唑替尼)与这些生物标志物的相关性最强,表明它们有可能成为治疗OSCC的关键药物。此外,通过qRT-PCR和免疫组织化学分析验证了这一发现,结果与RNA-seq数据一致。结论:ANPEP、APOB、GLP1R和SI被确定为潜在的OSCC生物标志物,为进一步的研究和治疗开发提供了有价值的见解。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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