Three distinct genomic subtypes of head and neck squamous cell carcinoma associated with clinical outcomes
Three distinct genomic subtypes of head and neck squamous cell carcinoma associated with clinical outcomes
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DOI：
10.1016/j.oraloncology.2018.08.009
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发表时间：
2018-10-01
期刊：
影响因子：
4.8
通讯作者：
Lee, Ju-Seog
中科院分区：
文献类型：
--
作者：
Lee, Dong Jin;Eun, Young-Gyu;Lee, Ju-Seog
目的：头颈部鳞状细胞癌(HNSCCs)的异质性导致类似癌症分期的患者的预后不可预测。除了人乳头瘤病毒(HPV)的作用外，还没有建立起HNSCCs的有效分子标记。因此，需要临床相关的分子亚型来优化HNSCC的治疗。本研究的目的是确定与临床预后相关的具有不同生物学特征的HNSCC亚型，并描述最能反映每个亚型生物学和临床特征的基因组变化。材料和方法：我们分析了包括宫颈SCC、食道SCC、肺SCC和HNSCC(n=1346)在内的泛鳞状细胞癌组织的基因表达谱数据，以评估SCC之间的异同，并确定与预后相关的HNSCC分子亚型。亚型特异性基因表达特征被识别并用于构建预测模型。在两个独立的队列中验证了亚型与预后的相关性。结果：PAN-SCC分析确定了三种新的HNSCC亚型。亚型1预后最好，与宫颈鳞癌相似，亚型3预后最差，与肺鳞状细胞癌相似。亚型2预后较差。在两个独立的验证队列中，与这三个亚型相关的600基因签名显著预测预后。这三种亚型也与免疫治疗的潜在益处相关。结论：我们确定了三种临床相关的HNSCC分子亚型。有必要进行独立的前瞻性研究，以评估亚型和相关基因标记的临床实用性。
Objectives: Heterogeneity of head and neck squamous cell carcinomas (HNSCCs) results in unpredictable outcomes for patients with similar stages of cancer. Beyond the role of human papilloma virus (HPV), no validated molecular marker of HNSCCs has been established. Thus, clinically relevant molecular subtypes are needed to optimize HNSCC therapy. The purpose of this study was to identify subtypes of HNSCC that have distinct biological characteristics associated with clinical outcomes and to characterize genomic alterations that best reflect the biological and clinical characteristics of each subtype.Materials and methods: We analyzed gene expression profiling data from pan-SCC tissues including cervical SCC, esophageal SCC, lung SCC, and HNSCC (n = 1346) to assess the similarities and differences among SCCs and to identify molecular subtypes of HNSCC associated with prognosis. Subtype-specific gene expression signatures were identified and used to construct predictive models. The association of the subtypes with prognosis was validated in two independent cohorts of patients.Results: Pan-SCC analysis identified three novel subtypes of HNSCC. Subtype 1 had the best prognosis and was similar to cervical SCC, whereas subtype 3 had the worst prognosis and was similar to lung SCC. Subtype 2 had a moderate prognosis. The 600-gene signature associated with the three subtypes significantly predicted prognosis in two independent validation cohorts. These three subtypes also were associated with potential benefit of immunotherapy.Conclusion: We identified three clinically relevant HNSCC molecular subtypes. Independent prospective studies to assess the clinical utility of the subtypes and associated gene signature are warranted.