Department of Gynecology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 København Ø, Denmark; Department of Gynecology and Obstetrics, Odense University Hospital, J.B. Winsløws Vej 4, 5000 Odense.
Department of Pathology, unit of Molecular Medicine, Herlev University Hospital.
Cancer Genet. 2023 Nov;278-279:9-16. doi: 10.1016/j.cancergen.2023.08.001. Epub 2023 Aug 3.
Ovarian Clear cell carcinomas (OCCC) are characterized by low response to chemotherapy and a poor prognosis in advanced stages. Several studies have demonstrated that OCCC are heterogenous entities. We have earlier identified four molecular profiles based on the mutational status of ARID1A and PIK3CA. In this study we aimed to examine the association between molecular profiles, Tumor Mutational Burden (TMB), and molecular signatures with the clinical outcome in OCCC METHODS: We identified 55 OCCC cases with corresponding data and biological tissue samples in the Danish Gynecological Cancer Database during 2005-2016. Mutational profiling and TMB were performed using the Oncomine Tumor Mutational Load Assay. Chi-square and Cox regression analyses were used. P-values < 0.05 were considered statistically significant.
Mutations in the PIK3CA gene (p=0.04) and low TMB (p=0.05) were associated with disease progression. In multivariate analyses adjusted for stage, patients with tumor mutations in the ARID1A and/or PIK3CA genes had a significantly impaired Progression Free Survival (PFS) and Overall Survival (OS) compared to patients who were wildtype ARID1A and PIK3CA (undetermined subgroup) (HR= 5.42 and HR= 2.77, respectively). High TMB status was associated with an improved PFS (HR= 0.36) and OS (HR= 0.46). A trend towards an improved PFS in patients with APOBEC enrichment was observed (HR 0.45).
TMB-High was associated with decreased risk of progression and with an improved PFS and OS. Furthermore, OCCC with mutations in either ARID1A and/or PIK3CA genes had a significantly impaired prognosis compared to the undetermined subgroup in stage adjusted analyses.
卵巢透明细胞癌（OCCC）的特点是对化疗反应低，晚期预后差。多项研究表明，OCCC 是异质性实体。我们之前根据 ARID1A 和 PIK3CA 的突变状态确定了四个分子谱。在这项研究中，我们旨在研究分子谱、肿瘤突变负担（TMB）和分子特征与 OCCC 临床结果之间的关系。
我们在 2005-2016 年期间在丹麦妇科癌症数据库中确定了 55 例具有相应数据和生物组织样本的 OCCC 病例。使用 Oncomine 肿瘤突变负荷分析进行突变分析和 TMB 分析。使用卡方检验和 Cox 回归分析。P 值<0.05 被认为具有统计学意义。
PIK3CA 基因的突变（p=0.04）和低 TMB（p=0.05）与疾病进展相关。在调整为分期的多变量分析中，与 ARID1A 和/或 PIK3CA 基因肿瘤突变的患者相比，野生型 ARID1A 和 PIK3CA 的患者无进展生存期（PFS）和总生存期（OS）明显受损（分别为 HR=5.42 和 HR=2.77）（未确定亚组）。高 TMB 状态与 PFS（HR=0.36）和 OS（HR=0.46）的改善相关。观察到 APOBEC 富集患者的 PFS 改善趋势（HR 0.45）。
TMB-高与进展风险降低以及 PFS 和 OS 改善相关。此外，在调整分期的分析中，与未确定亚组相比，ARID1A 和/或 PIK3CA 基因发生突变的 OCCC 患者的预后明显受损。
