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头颈部鳞状细胞癌中的二硫化物依赖性细胞程序性坏死:综合生物信息学与体外分析

Disulfidptosis in head and neck squamous carcinoma: Integrative bioinformatic and in-vitro analysis.

作者信息

Huang Xufeng, Yang Jinyan, Wang Qi, Fu Rao, Wen Xutao, Li Zhengrui, Zhang Ling

机构信息

Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.

School of Stomatology, Southwest Medical University, Luzhou, China.

出版信息

Oral Dis. 2024 Nov;30(8):4993-5006. doi: 10.1111/odi.14977. Epub 2024 May 2.

Abstract

BACKGROUND

Head and neck squamous carcinoma (HNSC) is a prevalent global malignancy with limited treatment options, which necessitates the development of novel therapeutic strategies. Disulfidptosis, a recently discovered and unique cell death pathway, may offer promise as a treatment target in HNSC.

MATERIALS AND METHODS

We identified disulfidptosis-related genes (DRGs) using multiple algorithms and developed a prognostic model based on a disulfidptosis-related gene index (DRGI). The model's predictive accuracy was assessed by ROC-AUC, and patients were stratified by risk scores. We investigated the tumor immune microenvironment, immune responses, tumorigenesis pathways, and chemotherapy sensitivity (IC50). We also constructed a diagnostic model using 20 machine-learning algorithms and validated PCBP2 expression through RT-qPCR and western blot.

RESULTS

We developed a 12-DRG DRGI prognostic model, classifying patients into high- and low-risk groups, with the high-risk group experiencing poorer clinical outcomes. Notable differences in tumor immune microenvironment and chemosensitivity were observed, with reduced immune activity and suboptimal treatment responses in the high-risk group. Advanced machine learning and in-vitro experiments supported DRGI's potential as a reliable HNSC diagnostic biomarker.

CONCLUSION

We established a novel DRGI-based prognostic and diagnostic model for HNSC, exploring its tumor immune microenvironment implications, and offering valuable insights for future research and clinical trials.

摘要

背景

头颈部鳞状细胞癌(HNSC)是一种全球普遍存在的恶性肿瘤,治疗选择有限,因此需要开发新的治疗策略。二硫化物诱导的细胞死亡(Disulfidptosis)是一种最近发现的独特细胞死亡途径,可能有望成为HNSC的治疗靶点。

材料与方法

我们使用多种算法鉴定了二硫化物诱导的细胞死亡相关基因(DRGs),并基于二硫化物诱导的细胞死亡相关基因指数(DRGI)建立了一个预后模型。通过ROC-AUC评估该模型的预测准确性,并根据风险评分对患者进行分层。我们研究了肿瘤免疫微环境、免疫反应、肿瘤发生途径和化疗敏感性(IC50)。我们还使用20种机器学习算法构建了一个诊断模型,并通过RT-qPCR和蛋白质免疫印迹验证了PCBP2的表达。

结果

我们开发了一个包含12个DRG的DRGI预后模型,将患者分为高风险组和低风险组,高风险组的临床结局较差。观察到肿瘤免疫微环境和化疗敏感性存在显著差异,高风险组的免疫活性降低且治疗反应不理想。先进的机器学习和体外实验支持DRGI作为可靠的HNSC诊断生物标志物的潜力。

结论

我们建立了一种基于DRGI的新型HNSC预后和诊断模型,探讨了其对肿瘤免疫微环境的影响,并为未来的研究和临床试验提供了有价值的见解。

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