Wang Chen, Armasu Sebastian M, Kalli Kimberly R, Maurer Matthew J, Heinzen Ethan P, Keeney Gary L, Cliby William A, Oberg Ann L, Kaufmann Scott H, Goode Ellen L
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Department of Oncology, Mayo Clinic, Rochester, Minnesota.
Clin Cancer Res. 2017 Aug 1;23(15):4077-4085. doi: 10.1158/1078-0432.CCR-17-0246. Epub 2017 Mar 9.
Here we assess whether molecular subtyping identifies biological features of tumors that correlate with survival and surgical outcomes of high-grade serous ovarian cancer (HGSOC). Consensus clustering of pooled mRNA expression data from over 2,000 HGSOC cases was used to define molecular subtypes of HGSOCs. This classification scheme was then applied to 381 Mayo Clinic HGSOC patients with detailed survival and surgical outcome information. Five molecular subtypes of HGSOC were identified. In the pooled dataset, three subtypes were largely concordant with prior studies describing proliferative, mesenchymal, and immunoreactive tumors (concordance > 70%), and the group of tumors previously described as differentiated type was segregated into two new types, one of which (anti-mesenchymal) had downregulation of genes that were typically upregulated in the mesenchymal subtype. Molecular subtypes were significantly associated with overall survival ( < 0.001) and with rate of optimal surgical debulking (≤1 cm, = 1.9E-4) in the pooled dataset. Among stage III-C or IV Mayo Clinic patients, molecular subtypes were also significantly associated with overall survival ( = 0.001), as well as rate of complete surgical debulking (no residual disease; 16% in mesenchymal tumors compared with >28% in other subtypes; = 0.02). HGSOC tumors may be categorized into five molecular subtypes that associate with overall survival and the extent of residual disease following debulking surgery. Because mesenchymal tumors may have features that were associated with less favorable surgical outcome, molecular subtyping may have future utility in guiding neoadjuvant treatment decisions for women with HGSOC. .
在此，我们评估分子亚型是否能识别出与高级别浆液性卵巢癌（HGSOC）的生存率和手术结果相关的肿瘤生物学特征。我们使用来自2000多例HGSOC病例的汇总mRNA表达数据进行共识聚类，以定义HGSOC的分子亚型。然后将该分类方案应用于381例梅奥诊所的HGSOC患者，这些患者具有详细的生存和手术结果信息。我们识别出了HGSOC的五种分子亚型。在汇总数据集中，三种亚型在很大程度上与先前描述增殖性、间充质性和免疫反应性肿瘤的研究一致（一致性>70%），并且先前被描述为分化型的肿瘤组被分为两种新类型，其中一种（抗间充质）具有在间充质亚型中通常上调的基因的下调。在汇总数据集中，分子亚型与总生存率（<0.001）以及最佳手术减瘤率（≤1 cm，=1.9E-4）显著相关。在梅奥诊所的III - C期或IV期患者中，分子亚型也与总生存率（=0.001）以及完全手术减瘤率显著相关（无残留疾病；间充质肿瘤中为16%，而其他亚型中>28%；=0.02）。HGSOC肿瘤可分为五种与总生存率和减瘤手术后残留疾病程度相关的分子亚型。由于间充质肿瘤可能具有与不太有利的手术结果相关的特征，分子亚型在指导HGSOC女性患者的新辅助治疗决策方面可能具有未来的应用价值。
