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用于改善口腔鳞状细胞癌预后预测并从单细胞水平指示基因靶点的新型铁死亡特征。

Novel ferroptosis signature for improving prediction of prognosis and indicating gene targets from single-cell level in oral squamous cell carcinoma.

作者信息

Tang Zhengming, Chen Yuanxin, Huang Yisheng, Zhao JianJiang, Jia Bo

机构信息

Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China.

Shenzhen Stomatological Hospital, Southern Medical University, Shenzhen, China.

出版信息

Heliyon. 2024 May 22;10(11):e31676. doi: 10.1016/j.heliyon.2024.e31676. eCollection 2024 Jun 15.

Abstract

BACKGROUND

Oral squamous cell carcinoma (OSCC) is one of the most prevalent kinds of cancers. Therefore, there is a pressing need to create a new risk scoring model to personalize the prognosis of OSCC patients and screen for patient-specific therapeutic agents and molecular targets.

METHODS

Firstly, A series of bioinformatics was performed to construct a novel ferroptosis-related prognostic model; Further, drug sensitivity analysis was used to screen for specific therapeutic agents for OSCC; Single-cell analysis was employed to investigate the enrichment of FRDEGs (ferroptosis-related differentially expressed genes) in the OSCC microenvironment; Finally, various experiments were conducted to screen and validate molecular therapeutic targets for OSCC.

RESULTS

In this study, we constructed a novel 10-FRDEGs risk scoring model. Base on the risk scoring model, we founded three potential chemotherapeutic agents for OSCC: 5Z)-7-Oxozeaenol, AT-7519, KIN001-266; In addition, FRDEGs were enriched in the epithelial cells of OSCC. Finally, we found that CA9 and CAV1 could regulate OSCC proliferation, migration and ferroptosis in vitro.

CONCLUSION

A novel 10-FRDEGs risk scoring model can predict the prognosis of patients with OSCC.Further,5Z)-7-Oxozeaenol, AT-7519, KIN001-266 are potential chemotherapeutic agents for OSCC.Moreover, we identified CA9、CAV1 as potential molecular target for the treatment of OSCC.Our findings provide new directions for prognostic assessment and precise treatment of oral cell squamous carcinoma.

摘要

背景

口腔鳞状细胞癌(OSCC)是最常见的癌症类型之一。因此,迫切需要创建一种新的风险评分模型,以实现OSCC患者预后的个性化,并筛选针对特定患者的治疗药物和分子靶点。

方法

首先,进行一系列生物信息学分析以构建一种新型的铁死亡相关预后模型;进一步地,利用药物敏感性分析筛选OSCC的特异性治疗药物;采用单细胞分析研究铁死亡相关差异表达基因(FRDEGs)在OSCC微环境中的富集情况;最后,进行各种实验以筛选和验证OSCC的分子治疗靶点。

结果

在本研究中,我们构建了一种新型的10-FRDEGs风险评分模型。基于该风险评分模型,我们发现了三种针对OSCC的潜在化疗药物:(5Z)-7-氧代玉米烯醇、AT-7519、KIN001-266;此外,FRDEGs在OSCC的上皮细胞中富集。最后,我们发现碳酸酐酶9(CA9)和小窝蛋白1(CAV1)在体外可调节OSCC的增殖、迁移和铁死亡。

结论

一种新型的10-FRDEGs风险评分模型可预测OSCC患者的预后。此外,(5Z)-7-氧代玉米烯醇、AT-7519、KIN001-266是OSCC的潜在化疗药物。而且,我们确定CA9、CAV1为OSCC治疗的潜在分子靶点。我们的研究结果为口腔鳞状细胞癌的预后评估和精准治疗提供了新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c7/11153103/c39f980278a7/gr1.jpg

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