Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany.
Molecular Health, Kurfuersten-Anlage 21, Heidelberg, 69115, Germany.
J Cancer Res Clin Oncol. 2024 Jul 25;150(7):367. doi: 10.1007/s00432-024-05901-4.
Endometrial cancer (EC) is heterogeneous with respect to epidemiology, clinical course, histopathology and tumor biology. Recently, The Cancer Genome Atlas (TCGA) network has identified four molecular subtypes with distinct clinical courses by an integrated multi-omics approach. These subtypes are of critical importance in the clinical management of EC. However, determination of TCGA molecular subtypes requires a complex methodological approach that is resource intensive and difficult to implement in diagnostic routine procedures. In this context, Talhouk et al. reported the precise determination of modified subtypes based on molecular surrogates obtained by a two-method approach comprising immunohistochemistry and DNA-sequence analysis (Proactive Molecular Risk Classifier for Endometrial Cancer; ProMisE). In this study, we aimed to identify EC molecular subtypes in analogy to TCGA and ProMisE applying an innovative whole exome-sequencing (WES) based single-method approach.
WES was performed in a cohort comprising N = 114 EC patients. WES data were analyzed using the oncology treatment decision support software MH Guide (Molecular Health, Heidelberg, Germany) and EC molecular subtypes in analogy to TCGA and ProMisE were determined. Results from both classifications were compared regarding their prognostic values using overall survival and progression-free survival analyses.
Applying a single-method WES-approach, EC molecular subtypes analogue to TCGA and ProMisE were identified in the study cohort. The surrogate marker-analogue classification precisely identified high-risk and low-risk EC, whereas the TCGA-analogue classification failed to obtain significant prognostic values in this regard.
Our data demonstrate that determination of EC molecular subtypes analogue to TCGA and ProMisE is feasible by using a single-method WES approach. Within our EC cohort, prognostic implications were only reliably provided by applying the surrogate marker-analogue approach. Designation of molecular subtypes in EC will be increasingly important in routine clinical practice. Thus, the single-method WES approach provides an important simple tool to tailor therapeutic decisions in EC.
子宫内膜癌（EC）在流行病学、临床过程、组织病理学和肿瘤生物学方面具有异质性。最近，癌症基因组图谱（TCGA）网络通过综合多组学方法，确定了具有不同临床过程的四个分子亚型。这些亚型对于 EC 的临床管理至关重要。然而，确定 TCGA 分子亚型需要一种复杂的方法，这种方法需要大量的资源，并且难以在诊断常规程序中实施。在这种情况下，Talhouk 等人报道了通过包括免疫组织化学和 DNA 序列分析的两方法方法获得的分子替代物来精确确定修改后的亚型，该方法称为子宫内膜癌主动分子风险分类器（ProMisE）。在这项研究中，我们旨在通过应用创新的全外显子测序（WES）单方法来模拟 TCGA 和 ProMisE 来识别 EC 分子亚型。
对包括 N=114 名 EC 患者的队列进行 WES。使用肿瘤治疗决策支持软件 MH Guide（Molecular Health，德国海德堡）分析 WES 数据，并模拟 TCGA 和 ProMisE 确定 EC 分子亚型。使用总生存期和无进展生存期分析比较两种分类的预后价值。
在研究队列中，应用单一方法 WES 方法，模拟 TCGA 和 ProMisE 的 EC 分子亚型被识别。替代标志物模拟分类精确地识别了高危和低危 EC，而 TCGA 模拟分类在这方面未能获得显著的预后价值。
我们的数据表明，通过使用单一方法 WES 方法，模拟 TCGA 和 ProMisE 的 EC 分子亚型的确定是可行的。在我们的 EC 队列中，仅通过应用替代标志物模拟方法才能可靠地提供预后意义。在常规临床实践中，EC 分子亚型的指定将变得越来越重要。因此，单一方法 WES 方法为 EC 中的治疗决策提供了重要的简单工具。
