Ovarian cancer (OC) is the most lethal gynaecological cancer with genomic complexity and extensive heterogeneity. This study aimed to characterize the molecular features of OC based on the gene expression profile of 2752 previously characterized metabolism-relevant genes and provide new strategies to improve the clinical status of patients with OC. Finally, three molecular subtypes (C1, C2 and C3) were identified. The C2 subtype displayed the worst prognosis, upregulated immune-cell infiltration status and expression level of immune checkpoint genes, lower burden of copy number gains and losses and suboptimal response to targeted drug bevacizumab. The C1 subtype showed downregulated immune-cell infiltration status and expression level of immune checkpoint genes, the lowest incidence of BRCA mutation and optimal response to targeted drug bevacizumab. The C3 subtype had an intermediate immune status, the highest incidence of BRCA mutation and a secondary optimal response to bevacizumab. Gene signatures of C1 and C2 subtypes with an opposite expression level were mainly enriched in proteolysis and immune-related biological process. The C3 subtype was mainly enriched in the T cell-related biological process. The prognostic and immune status of subtypes were validated in the Gene Expression Omnibus (GEO) dataset, which was predicted with a 45-gene classifier. These findings might improve the understanding of the diversity and therapeutic strategies for OC.

中文翻译：

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卵巢癌代谢相关分子亚型的鉴定

卵巢癌（OC）是最致命的妇科癌症，具有基因组复杂性和广泛的异质性。本研究旨在基于 2752 个先前表征的代谢相关基因的基因表达谱来表征 OC 的分子特征，并提供改善 OC 患者临床状况的新策略。最后，确定了三种分子亚型（C1、C2 和 C3）。C2 亚型预后最差，免疫细胞浸润状态和免疫检查点基因表达水平上调，拷贝数增减负担较低，对靶向药物贝伐单抗反应欠佳。C1亚型显示出下调的免疫细胞浸润状态和免疫检查点基因的表达水平，BRCA 突变发生率最低，对靶向药物贝伐单抗的反应最佳。C3 亚型具有中等免疫状态、最高的 BRCA 突变发生率和对贝伐单抗的次要最佳反应。具有相反表达水平的 C1 和 C2 亚型的基因特征主要富集在蛋白水解和免疫相关的生物学过程中。C3亚型主要富集于T细胞相关的生物学过程。亚型的预后和免疫状态在基因表达综合 (GEO) 数据集中得到验证，该数据集使用 45 基因分类器进行预测。这些发现可能会提高对 OC 的多样性和治疗策略的理解。具有相反表达水平的 C1 和 C2 亚型的基因特征主要富集在蛋白水解和免疫相关的生物学过程中。C3亚型主要富集于T细胞相关的生物学过程。亚型的预后和免疫状态在基因表达综合 (GEO) 数据集中得到验证，该数据集使用 45 基因分类器进行预测。这些发现可能会提高对 OC 的多样性和治疗策略的理解。具有相反表达水平的 C1 和 C2 亚型的基因特征主要富集在蛋白水解和免疫相关的生物学过程中。C3亚型主要富集于T细胞相关的生物学过程。亚型的预后和免疫状态在基因表达综合 (GEO) 数据集中得到验证，该数据集使用 45 基因分类器进行预测。这些发现可能会提高对 OC 的多样性和治疗策略的理解。