Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
Br J Cancer. 2024 Apr;130(7):1176-1186. doi: 10.1038/s41416-024-02579-w. Epub 2024 Jan 27.
Nasopharyngeal carcinoma (NPC) treatment is largely based on a 'one-drug-fits-all' strategy in patients with similar pathological characteristics. However, given its biological heterogeneity, patients at the same clinical stage or similar therapies exhibit significant clinical differences. Thus, novel molecular subgroups based on these characteristics may better therapeutic outcomes.
Herein, 192 treatment-naïve NPC samples with corresponding clinicopathological information were obtained from Fujian Cancer Hospital between January 2015 and January 2018. The gene expression profiles of the samples were obtained by RNA sequencing. Molecular subtypes were identified by consensus clustering. External NPC cohorts were used as the validation sets.
Patients with NPC were classified into immune, metabolic, and proliferative molecular subtypes with distinct clinical features. Additionally, this classification was repeatable and predictable as validated by the external NPC cohorts. Metabolomics has shown that arachidonic acid metabolites were associated with NPC malignancy. We also identified several key genes in each subtype using a weighted correlation network analysis. Furthermore, a prognostic risk model based on these key genes was developed and was significantly associated with disease-free survival (hazard ratio, 1.11; 95% CI, 1.07-1.16; P < 0.0001), which was further validated by an external NPC cohort (hazard ratio, 7.71; 95% CI, 1.39-42.73; P < 0.0001). Moreover, the 1-, 3-, and 5-year areas under the curve were 0.84 (95% CI, 0.74-0.94), 0.81 (95% CI, 0.73-0.89), and 0.82 (95% CI, 0.73-0.90), respectively, demonstrating a high predictive value.
Overall, we defined a novel classification of nasopharyngeal carcinoma (immune, metabolism, and proliferation subtypes). Among these subtypes, metabolism and proliferation subtypes were associated with advanced stage and poor prognosis of NPC patients, whereas the immune subtype was linked to early stage and favorable prognosis.
鼻咽癌（NPC）的治疗在很大程度上基于具有相似病理特征的患者的“一刀切”策略。然而，鉴于其生物学异质性，相同临床阶段或类似治疗的患者表现出显著的临床差异。因此，基于这些特征的新型分子亚组可能会带来更好的治疗效果。
本研究纳入了 192 例来自福建肿瘤医院于 2015 年 1 月至 2018 年 1 月间初治的 NPC 患者的样本，并获取了相应的临床病理信息。通过 RNA 测序获得样本的基因表达谱。采用共识聚类法鉴定分子亚型。外部 NPC 队列被用作验证集。
将 NPC 患者分为免疫、代谢和增殖分子亚型，具有不同的临床特征。此外，通过外部 NPC 队列验证，该分类具有可重复性和可预测性。代谢组学研究表明，花生四烯酸代谢物与 NPC 的恶性程度相关。我们还使用加权相关网络分析鉴定了每种亚型中的几个关键基因。此外，还基于这些关键基因建立了一个预后风险模型，该模型与无病生存率显著相关（风险比 1.11；95%CI，1.07-1.16；P<0.0001），并通过外部 NPC 队列进一步验证（风险比 7.71；95%CI，1.39-42.73；P<0.0001）。此外，1、3 和 5 年的曲线下面积分别为 0.84（95%CI，0.74-0.94）、0.81（95%CI，0.73-0.89）和 0.82（95%CI，0.73-0.90），表明具有较高的预测价值。
总之，我们定义了一种新的鼻咽癌分类（免疫、代谢和增殖亚型）。在这些亚型中，代谢和增殖亚型与 NPC 患者的晚期和预后不良相关，而免疫亚型与早期和预后良好相关。
