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微卫星不稳定性和杂合性丢失作为口腔鳞状细胞癌的预后标志物:分子机制、检测技术和治疗策略。

Microsatellite Instability and Loss of Heterozygosity as Prognostic Markers in Oral Squamous Cell Carcinoma: Molecular Mechanisms, Detection Techniques, and Therapeutic Strategies.

机构信息

Faculty of Science, Department of Biology, Gazi University, Ankara, Turkey.

Faculty of Dentistry, Department of Oral Pathology, Gazi University, Ankara, Turkey.

出版信息

Genes Chromosomes Cancer. 2024 Oct;63(10):e70002. doi: 10.1002/gcc.70002.

DOI:10.1002/gcc.70002
PMID:39470253
Abstract

The aim of this study was to conduct a systematic review of research investigating the potential role of microsatellite instability (MSI) and loss of heterozygosity (LOH) in oral squamous cell carcinoma (OSCC), with a focus on molecular mechanisms, detection methods, and therapeutic approaches. Search for articles involved the PubMed and Scopus. Previous retrospective and prospective studies identified variations between oral cancers that exhibit microsatellite stability and LOH. In this search, 294 articles were initially retrieved. Of these, 70 were excluded due to duplication, 106 were identified as ineligible by automated tools, and 24 were excluded as they were published in languages other than English. An additional 94 articles were excluded, 32 of which focused on head and neck cancers broadly, and 8 could not be accessed due to withdrawal. Ultimately, a systematic review was conducted based on 54 selected articles. Among the chromosomes analyzed for MSI and LOH, the highest frequency of LOH was observed on chromosome 9p. The MSI subtype is particularly susceptible to immunotherapeutic methods, such as the use of anti-PD-L1 and anti-CTLA4 antibodies, owing to its strong immunogenicity and ubiquitous expression of immune checkpoint ligands. Given the distinct characteristics and clinical behavior of oral cancer with MSI compared to microsatellite stable disease, it is advisable to incorporate MSI testing into the diagnostic process for all stages of tumor development. This ensured that each patient had received precise and effective treatment.

摘要

本研究旨在对研究口腔鳞状细胞癌(OSCC)中微卫星不稳定性(MSI)和杂合性丢失(LOH)潜在作用的文献进行系统综述,重点关注分子机制、检测方法和治疗方法。搜索文章涉及 PubMed 和 Scopus。先前的回顾性和前瞻性研究发现,表现出微卫星稳定和 LOH 的口腔癌之间存在差异。在本次搜索中,最初检索到 294 篇文章。其中 70 篇因重复而被排除,106 篇因自动化工具被认定为不合格,24 篇因发表的语言不是英语而被排除。另外排除了 94 篇文章,其中 32 篇文章广泛关注头颈部癌症,8 篇文章因撤回而无法获取。最终,根据 54 篇选定的文章进行了系统综述。在分析 MSI 和 LOH 的染色体中,9p 染色体上的 LOH 频率最高。MSI 亚型特别容易受到免疫治疗方法的影响,例如使用抗 PD-L1 和抗 CTLA4 抗体,因为其具有强烈的免疫原性和免疫检查点配体的普遍表达。鉴于 MSI 口腔癌与微卫星稳定疾病相比具有独特的特征和临床行为,建议将 MSI 检测纳入肿瘤发展的所有阶段的诊断过程。这确保了每位患者都接受了精确有效的治疗。

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