Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.
J Pathol Clin Res. 2024 Sep;10(5):e12391. doi: 10.1002/2056-4538.12391.
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.
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，特别是其对预后和免疫微环境的影响，尚未得到充分探讨。全面了解 HRD 状态可以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 NPC 中的 HRD 状态：来自本地收集的珠江队列和来自公共数据集的香港 (SRA288429) 和新加坡 (SRP035573) 队列。我们采用 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 突变，以及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，具有阴性 HRD 状态（无 HRD）的个体复发风险更高 [风险比 (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，他们的死亡率更高 (HR，26.04；95%CI，1.43-34.21；p=0.016)。体外实验表明，BRCA1 敲低的 NPC 细胞对放化疗更敏感。此外，HRD 组的肿瘤突变负担和肿瘤新抗原负担水平明显高于无 HRD 组。免疫浸润分析表明，HRD 组织具有非炎症性肿瘤微环境。总之，HRD 患者在 NPC 中表现出相对较好的预后，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，可以选择更精确和有效的治疗方法，并在一定程度上有助于预测治疗反应和预后。
