BACKGROUND Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer (EOC) with distinct pathological, biological, and molecular features. OCCCs are more resistant to conventional treatment regimen of EOC and have the worst stage-adjusted prognosis amongst EOC subtypes. As the OCCC incidence rate in Asian populations has significantly increased in recent decades, it is critical to elucidate its molecular features that could lead to OCCC-tailored therapeutic strategies. METHODS Gene expression profiles of 222 OCCC were analyzed by hierarchical clustering and statistical analyses. FINDINGS We identified two OCCC gene expression subtypes: EpiCC-epithelial-like, which is associated with early-stage disease, with a relatively higher rate of gene mutations in the SWI/SNF complex; and MesCC-mesenchymal-like, associated with late-stage and higher enrichment of immune-related pathway activity. Genetic, copy number and transcriptomic analyses showed that both EpiCC and MesCC carried OCCC-associated aberrations. The EpiCC/MesCC classification was reproducible in validation cohorts and OCCC cell lines. MesCC tumors had a poorer progression-free survival (PFS) than EpiCC tumors (HR: 3·0, p = 0·0006). Functional assays in cell lines showed that the MesCC subtype was more proliferative and more anoikis-resistant than the EpiCC. By applying the EpiCC/MesCC classification to the TCGA renal clear cell carcinoma cohort, our results indicated interoperability of the subtyping scheme, and revealed preferential drug response of MesCC to bevacizumab. INTERPRETATION The EpiCC/MesCC classification shows promise for prognostic and therapeutic stratification in OCCC patients and warrants further investigation in the context of OCCC gene expression subtype-tailored treatment strategies.

中文翻译：

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基因表达特征的分析确定了预后的和功能上不同的卵巢透明细胞癌亚型。

背景技术卵巢透明细胞癌（OCCC）是上皮性卵巢癌（EOC）的组织学亚型，具有独特的病理学，生物学和分子学特征。OCCC对EOC的常规治疗方案更具抵抗力，并且在EOC亚型中，经阶段调整的预后最差。由于近几十年来亚洲人群的OCCC发病率显着增加，因此阐明其分子特征可能导致OCCC量身定制的治疗策略至关重要。方法采用分级聚类和统计分析方法，对222例OCCC的基因表达谱进行分析。研究发现，我们发现了两种OCCC基因表达亚型：EpiCC-上皮样，与早期疾病有关，在SWI / SNF复合体中基因突变的发生率相对较高。和类似MesCC的间充质 与晚期和更高水平的免疫相关途径活性相关。遗传，拷贝数和转录组分析表明EpiCC和MesCC均携带OCCC相关像差。EpiCC / MesCC分类在验证队列和OCCC细胞系中可重现。MesCC肿瘤的无进展生存期（PFS）比EpiCC肿瘤差（HR：3·0，p = 0·0006）。细胞系中的功能分析表明，MesCC亚型比EpiCC更具增殖性，并且对厌食症的耐受性更高。通过将EpiCC / MesCC分类应用于TCGA肾透明细胞癌队列，我们​​的结果表明该分型方案具有互操作性，并揭示了MesCC对贝伐单抗的优先药物反应。