同源重组缺陷(HRD)与较好的预后有关,并可能导致鼻咽癌的肿瘤微环境不发炎。

IF 3.4 2区 医学 Q1 PATHOLOGY
Xinyi Zhou, Haoxuan Ying, Yujie Sun, Wenda Zhang, Peng Luo, Shuhan Zhu, Jian Zhang
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引用次数: 0

摘要

同源重组缺陷(HRD)评分是基因组不稳定性的可靠指标。HRD在鼻咽癌(NPC)中的意义,尤其是对预后和免疫微环境的影响,还有待充分探讨。全面了解HRD状态可为指导精准治疗提供有价值的见解。我们利用三个队列来研究鼻咽癌的HRD状态:本地收集的珠江队列、公共数据集的香港队列(SRA288429)和新加坡队列(SRP035573)。我们采用了 GATK(基因组分析工具包)最佳实践流程来研究种系和体细胞 BRCA1/2 基因突变,并利用各种生物信息学工具和算法来研究 HRD 状态与临床分子特征之间的关联。我们发现,在珠江队列中,HRD 状态为阴性(no-HRD)的个体表现出更高的复发风险[危险比 (HR),1.43;95% 置信区间 (CI),2.03-333.76;p = 0.012],而在新加坡队列中,与 HRD 组相比,他们的死亡风险更高(HR,26.04;95% CI,1.43-34.21;p = 0.016)。体外实验表明,BRCA1基因敲除的鼻咽癌细胞对化疗放疗的敏感性更高。此外,HRD组的肿瘤突变负荷和肿瘤新抗原负荷水平明显高于无HRD组。免疫浸润分析表明,HRD 组织往往具有非炎症肿瘤微环境。总之,HRD 患者的预后相对较好,这可能与非炎症性免疫微环境有关。这些发现对治疗分层具有积极意义,有助于选择更精确、更有效的治疗方法,并在一定程度上有助于预测治疗反应和预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma

Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma

Homologous recombination deficiency (HRD) score is a reliable indicator of genomic instability. The significance of HRD in nasopharyngeal carcinoma (NPC), particularly its influence on prognosis and the immune microenvironment, has yet to be adequately explored. Understanding HRD status comprehensively can offer valuable insights for guiding precision treatment. We utilised three cohorts to investigate HRD status in NPC: the Zhujiang cohort from local collection and the Hong Kong (SRA288429) and Singapore (SRP035573) cohorts from public datasets. The GATK (genome analysis toolkit) best practice process was employed to investigate germline and somatic BRCA1/2 mutations and various bioinformatics tools and algorithms to examine the association between HRD status and clinical molecular characteristics. We found that individuals with a negative HRD status (no-HRD) exhibited a higher risk of recurrence [hazard ratio (HR), 1.43; 95% confidence interval (CI), 2.03–333.76; p = 0.012] in the Zhujiang cohort, whereas, in the Singapore cohort, they experienced a higher risk of mortality (HR, 26.04; 95% CI, 1.43–34.21; p = 0.016) compared with those in the HRD group. In vitro experiments demonstrated that NPC cells with BRCA1 knockdown exhibit heightened sensitivity to chemoradiotherapy. Furthermore, the HRD group showed significantly higher tumour mutational burden and tumour neoantigen burden levels than the no-HRD group. Immune infiltration analysis indicated that HRD tissues tend to have a non-inflamed tumour microenvironment. In conclusion, patients with HRD exhibit a comparatively favourable prognosis in NPC, possibly associated with a non-inflammatory immune microenvironment. These findings have positive implications for treatment stratification, enabling the selection of more precise and effective therapeutic approaches and aiding in the prediction of treatment response and prognosis to a certain extent.

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来源期刊
Journal of Pathology Clinical Research
Journal of Pathology Clinical Research Medicine-Pathology and Forensic Medicine
CiteScore
7.40
自引率
2.40%
发文量
47
审稿时长
20 weeks
期刊介绍: The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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