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高危 TP53 突变可预测头颈部鳞状细胞癌患者对初始治疗的反应较差。

High-risk TP53 mutations predict poor primary treatment response of patients with head and neck squamous cell carcinoma.

机构信息

Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Department of Clinical Specialist and Dental Sciences, Marche Polytechnic University, Ancona, Italy.

出版信息

Oral Dis. 2024 May;30(4):2018-2026. doi: 10.1111/odi.14698. Epub 2023 Jul 27.

Abstract

OBJECTIVES

Head and neck squamous cell carcinoma (HNSCC) poses a diagnostic and therapeutic challenge worldwide and is associated with a poor survival rate. Due to the variability in the efficacy of treatments for HNSCC, new predictive biomarkers of therapy outcomes are needed. Recently, we developed an algorithm that employs the mutational profile of TP53 as an independent prognostic factor in HNSCC. In this study, we investigated its role as a predictive biomarker of treatment outcomes in HNSCC patients. We also tested the usefulness of two classification systems for TP53 mutational landscapes.

MATERIALS AND METHODS

Clinical and genomic data were retrieved from The Cancer Genome Atlas database. We built a multivariate stepwise backward binary regression model to assess the role of TP53 mutations in predicting therapeutic outcomes.

RESULTS

Cases harbouring high-risk-of-death mutations reported an odds ratio of 3.301 for stable or progressive disease compared to wild-type cases, while no significant difference in treatment outcomes was found between cases with low-risk-of-death mutations and wild-type TP53. Our analysis found that older patients with a history of alcohol consumption had a higher risk of stable/progressive disease.

CONCLUSIONS

This study improves current evidence on the role of TP53 mutations in treatment response in HNSCC patients.

摘要

目的

头颈部鳞状细胞癌(HNSCC)在全球范围内构成了诊断和治疗的挑战,并且与生存率低有关。由于 HNSCC 治疗效果的可变性,因此需要新的治疗结果预测性生物标志物。最近,我们开发了一种算法,该算法将 TP53 的突变谱用作 HNSCC 的独立预后因素。在这项研究中,我们研究了其作为 HNSCC 患者治疗结果预测性生物标志物的作用。我们还测试了两种 TP53 突变景观分类系统的有用性。

材料和方法

从癌症基因组图谱数据库中检索了临床和基因组数据。我们建立了一个多变量逐步向后二元回归模型,以评估 TP53 突变在预测治疗结果中的作用。

结果

与野生型病例相比,携带高死亡风险突变的病例报告稳定或进展疾病的优势比为 3.301,而低死亡风险突变与野生型 TP53 的病例之间的治疗结果无明显差异。我们的分析发现,有饮酒史的老年患者患有稳定/进展性疾病的风险更高。

结论

这项研究提高了目前关于 TP53 突变在 HNSCC 患者治疗反应中的作用的证据。

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