TCGA molecular subtypes in endometriosis-associated ovarian cancer: a systematic review and meta-analysis

Endometriosis-associated ovarian cancer (EAOC) mainly includes endometrioid ovarian cancer (ENOC) and clear cell ovarian cancer (CCOC). The Cancer Genome Atlas (TCGA) revealed four molecular subtypes of endometrial cancer (EC) in 2013, which have been proven pivotal in the diagnostic, prognostic and therapeutic domains of EC. Existing evidence indicates that EC and EAOC molecular analysis have similar significance. This review aims to investigate the distribution, staging and prognostic characteristics of molecular subtypes in EAOC. PubMed, Embase and Web of Science were systematically searched from January 2013 to December 2023 using predefined keywords. Patient characteristics, including stage and prognostic characteristics, were extracted from the selected studies. Data analysis was carried out using Stata 14MP. A total of 6 studies involving 1,133 patients with ENOC and 4 studies comprising 377 patients with CCOC were included. ENOC had a higher frequency of the POLE mutation (POLEmut) subtype (odds ratio (OR) = 2.29, 95% CI: 1.03–5.11, p = 0.043) and the mismatch repair deficient (MMRd) subtype (OR = 3.54, 95% CI: 2.05–6.11, p = 0.000) than CCOC; ENOC had a lower frequency of the no specific molecular profile (NSMP) subtype (OR = 0.55, 95% CI: 0.41–0.73, p = 0.000) and the p53 abnormal (p53abn) subtype (OR = 0.97, 95% CI: 0.67–1.42, p = 0.893). The hazard ratios (HR) of the p53abn subtype in ENOC were disease-free survival (DFS) (HR = 3.25, 95% CI: 1.46–7.21, p = 0.004) and progression-free survival (PFS) (HR = 4.11, 95% CI: 2.86–5.92, p = 0.000). The DFS of the p53abn subtype in CCOC was calculated (HR = 5.52, 95% CI: 3.43–8.90, p = 0.000). The TCGA subtypes of EC may exhibit similarities in prognosis between ENOC and CCOC.子宫内膜异位症相关卵巢癌（Endometriosis-associated ovarian cancer, EAOC）主要涵盖子宫内膜样卵巢癌（endometrioid ovarian cancer, ENOC）与透明细胞卵巢癌（clear cell ovarian cancer, CCOC）。2013年，癌症基因组图谱（Cancer Genome Atlas, TCGA）确立了子宫内膜癌（endometrial cancer, EC）的四种分子亚型，该分型已被证实对子宫内膜癌的诊断、预后及治疗领域具有关键指导价值。现有研究证据表明，子宫内膜癌与EAOC的分子分型分析具有相似的临床意义。本综述旨在探讨EAOC分子亚型的分布特征、分期情况与预后特点。研究系统检索了2013年1月至2023年12月间PubMed、Embase及Web of Science数据库中符合预设关键词的相关文献。从纳入的研究中提取患者的基线特征（包括分期信息）与预后特征数据，并采用Stata 14MP统计软件完成数据分析。最终共纳入6项涉及1133例子宫内膜样卵巢癌患者的研究，以及4项涵盖377例透明细胞卵巢癌患者的研究。相较于透明细胞卵巢癌，子宫内膜样卵巢癌的POLE突变（POLEmut）亚型与错配修复缺陷（MMRd）亚型的检出率更高（比值比[OR]=2.29，95%置信区间[CI]：1.03~5.11，P=0.043；OR=3.54，95%CI：2.05~6.11，P=0.000），而无特定分子谱（NSMP）亚型与p53异常（p53abn）亚型的检出率更低（OR=0.55，95%CI：0.41~0.73，P=0.000；OR=0.97，95%CI：0.67~1.42，P=0.893）。在子宫内膜样卵巢癌中，p53异常亚型的无病生存期（DFS，HR=3.25，95%CI：1.46~7.21，P=0.004）与无进展生存期（PFS，HR=4.11，95%CI：2.86~5.92，P=0.000）的风险比均具有统计学意义。透明细胞卵巢癌中p53异常亚型的无病生存期风险比为HR=5.52，95%CI：3.43~8.90，P=0.000。子宫内膜癌的TCGA分子亚型在子宫内膜样卵巢癌与透明细胞卵巢癌中可能呈现相似的预后关联特征。