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鉴定口腔鳞状细胞癌中与内质网应激相关的具有优异预后和临床价值的预后风险模型。

Identification of an endoplasmic reticulum stress-related prognostic risk model with excellent prognostic and clinical value in oral squamous cell carcinoma.

机构信息

The Affiliated Stomatological Hospital of Nanchang University, Nanchang, Jiangxi, China.

The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi, China.

出版信息

Aging (Albany NY). 2023 Aug 25;15(19):10010-10030. doi: 10.18632/aging.204983.

Abstract

BACKGROUND

Recently, endoplasmic reticulum stress related gene (ERS) markers have performed very well in predicting the prognosis of tumor patients.

METHODS

The differentially expressed genes in Oral squamous cell carcinoma (OSCC) were obtained from TCGA and GTEx database. Three prognosis-related and differentially expressed ERSs were screened out by Least Absolute Selection and Shrinkage Operator (Lasso) regression to construct a prognostic risk model. Receiver Operating Characteristic Curve (ROC), riskplots and survival curves were used to verify the model's accuracy in predicting prognosis. Multi-omics analysis of immune infiltration, gene mutation, and stem cell characteristics were performed to explore the possible mechanism of OSCC. Finally, we discussed the model's clinical application value from the perspective of drug sensitivity.

RESULTS

Three genes used in the model (IBSP, RDM1, RBP4) were identified as prognostic risk factors. Bioinformatics analysis, tissue and cell experiments have fully verified the abnormal expression of these three genes in OSCC. Multiple validation methods and internal and external datasets confirmed the model's excellent performance in predicting and discriminating prognosis. Cox regression analysis identified risk score as an independent predictor of prognosis. Multi-omics analysis found strong correlations between risk scores and immune cells, cell stemness index, and tumor mutational burden (TMB). It was also observed that the risk score was closely related to the half maximal inhibitory concentration of docetaxel, gefitinib and erlotinib. The excellent performance of the nomogram has been verified by various means.

CONCLUSION

A prognostic model with high clinical application value was constructed. Immune cells, cellular stemness, and TMB may be involved in the progression of OSCC.

摘要

背景

最近,内质网应激相关基因(ERS)标志物在预测肿瘤患者预后方面表现出色。

方法

从 TCGA 和 GTEx 数据库中获取口腔鳞状细胞癌(OSCC)的差异表达基因。通过最小绝对收缩和选择算子(Lasso)回归筛选出三个与预后相关且差异表达的 ERS,构建预后风险模型。使用接收者操作特征曲线(ROC)、风险图和生存曲线验证模型预测预后的准确性。进行多组学分析以探索免疫浸润、基因突变和干细胞特征的可能机制。最后,从药物敏感性的角度探讨模型的临床应用价值。

结果

模型中使用的三个基因(IBSP、RDM1、RBP4)被鉴定为预后风险因素。生物信息学分析、组织和细胞实验充分验证了这三个基因在 OSCC 中的异常表达。多种验证方法和内部及外部数据集证实了该模型在预测和区分预后方面的出色性能。Cox 回归分析确定风险评分是预后的独立预测因子。多组学分析发现风险评分与免疫细胞、细胞干性指数和肿瘤突变负荷(TMB)之间存在强烈相关性。还观察到风险评分与多西他赛、吉非替尼和厄洛替尼的半最大抑制浓度密切相关。该列线图的优异性能已通过多种方式得到验证。

结论

构建了一个具有高临床应用价值的预后模型。免疫细胞、细胞干性和 TMB 可能参与 OSCC 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c76/10599730/cb3a200c32d4/aging-15-204983-g001.jpg

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