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口腔鳞状细胞癌中多胺相关特征及六种新型预后生物标志物的鉴定

Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma.

作者信息

Tang Jiezhang, Wu Xuechen, Cheng Bo, Lu Yajie

机构信息

Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan, China.

出版信息

Front Mol Biosci. 2023 Jan 17;10:1073770. doi: 10.3389/fmolb.2023.1073770. eCollection 2023.

Abstract

Elevated polyamine levels are required for tumor transformation and development; however, expression patterns of polyamines and their diagnostic potential have not been investigated in oral squamous cell carcinoma (OSCC), and its impact on prognosis has yet to be determined. A total of 440 OSCC samples and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Consensus clustering was conducted to classify OSCC patients into two subgroups based on the expression of the 17 polyamine regulators. Polyamine-related differentially expressed genes (PARDEGs) among distinct polyamine clusters were determined. To create a prognostic model, PARDEGs were examined in the training cohorts using univariate-Lasso-multivariate Cox regression analyses. Six prognostic genes, namely, "," "," "," "," ," and "," were identified and applied to develop a predictive model for OSCC. According to the median risk score, the patients were split into high-risk and low-risk groups. The predictive performance of the six gene models was proven by the ROC curve analysis of the training and validation cohorts. Kaplan-Meier curves revealed that the high-risk group had poorer prognosis. Furthermore, the low-risk group was more susceptible to four chemotherapy drugs according to the IC50 of the samples computed by the "pRRophetic" package. The correlation between the risk scores and the proportion of immune cells was calculated. Meanwhile, the tumor mutational burden (TMB) value of the high-risk group was higher. Real-time quantitative polymerase chain reaction was applied to verify the genes constructing the model. The possible connections of the six genes with various immune cell infiltration and therapeutic markers were anticipated. In conclusion, we identified a polyamine-related prognostic signature, and six novel biomarkers in OSCC, which may provide insights to identify new treatment targets for OSCC.

摘要

肿瘤转化和发展需要升高的多胺水平;然而,多胺的表达模式及其在口腔鳞状细胞癌(OSCC)中的诊断潜力尚未得到研究,其对预后的影响也尚未确定。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中获取了总共440个OSCC样本和临床数据。基于17种多胺调节因子的表达,进行一致性聚类以将OSCC患者分为两个亚组。确定了不同多胺簇之间的多胺相关差异表达基因(PARDEGs)。为了创建一个预后模型,在训练队列中使用单变量 - Lasso - 多变量Cox回归分析来检查PARDEGs。鉴定出六个预后基因,即“,”,“,”,“,”,“和”,“,”,并将其应用于开发OSCC的预测模型。根据中位风险评分,将患者分为高风险和低风险组。通过训练和验证队列的ROC曲线分析证明了六个基因模型的预测性能。Kaplan - Meier曲线显示高风险组预后较差。此外,根据“pRRophetic”软件包计算的样本IC50,低风险组对四种化疗药物更敏感。计算了风险评分与免疫细胞比例之间的相关性。同时,高风险组的肿瘤突变负担(TMB)值更高。应用实时定量聚合酶链反应来验证构建模型的基因。预测了这六个基因与各种免疫细胞浸润和治疗标志物之间可能的联系。总之,我们在OSCC中鉴定出一种多胺相关的预后特征和六个新的生物标志物,这可能为确定OSCC的新治疗靶点提供见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b3/9887031/092ba000dc3e/fmolb-10-1073770-g006.jpg

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