Identification and Verification of a Prognostic Risk Signature in Oral Squamous Cell Carcinoma.

IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Current topics in medicinal chemistry Pub Date : 2024-09-05 DOI:10.2174/0115680266335055240828061128
Rishou Chen, Junlin Duan, Yonglong Ye, Huan Xu, Yali Ding, Jun Liu
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引用次数: 0

Abstract

Introduction: Oral squamous cell carcinoma (OSCC) is a prevalent malignant condition. This study aimed to investigate the role of mTORC1 signaling and develop a prognostic model for OSCC.

Materials and methods: The single-sample gene set enrichment analysis (ssGSEA) algorithm was utilized to calculate the Z-Score of Hallmarks in OSCC, followed by univariate Cox regression analysis to identify processes associated with prognosis. Weighted gene co-expression network analysis (WGCNA) was performed using transcriptomic data from the cancer genome atlas (TCGA) cohort to identify genes correlated with mTORC1 signaling. A six-gene prognostic model was constructed using multifactorial Cox regression analysis and validated using an external dataset.

Results: The study uncovered a strong linkage between mTORC1, glycolysis, hypoxia, and the prognosis of OSCC. mTORC1 signaling emerged as the most significant risk factor, negatively impacting patient survival. Additionally, a six-gene prognostic risk score model was developed which provided a quantitative measure of patients' survival probabilities. Interestingly, within the context of these findings, TP53 gene mutations were predominantly observed in the high-risk group, potentially underlining the genetic complexity of this patient subgroup. Additionally, differential immune cell infiltration and an integrated nomogram were also reported.

Conclusion: This study highlights the importance of mTORC1 signaling in OSCC prognosis and presents a robust prognostic model for predicting patient outcomes.

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口腔鳞状细胞癌预后风险特征的识别与验证
简介口腔鳞状细胞癌(OSCC)是一种常见的恶性肿瘤。本研究旨在探讨mTORC1信号转导的作用,并建立OSCC的预后模型:利用单样本基因组富集分析(ssGSEA)算法计算OSCC标志物的Z-Score,然后进行单变量Cox回归分析,以确定与预后相关的过程。利用癌症基因组图谱(TCGA)队列中的转录组数据进行了加权基因共表达网络分析(WGCNA),以确定与mTORC1信号转导相关的基因。利用多因素考克斯回归分析构建了一个六基因预后模型,并利用外部数据集进行了验证:研究发现,mTORC1、糖酵解、缺氧与 OSCC 的预后之间存在密切联系。此外,研究人员还建立了一个六基因预后风险评分模型,对患者的生存概率进行量化测量。有趣的是,在这些研究结果中,TP53 基因突变主要出现在高危人群中,这可能凸显了这一患者亚群的遗传复杂性。此外,还报告了不同的免疫细胞浸润和综合提名图:本研究强调了mTORC1信号在OSCC预后中的重要性,并提出了一个预测患者预后的可靠模型。
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来源期刊
CiteScore
6.40
自引率
2.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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