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CDCA5 和 FOXM1 表达的综合模型结合残留疾病可预测卵巢癌患者的预后。

An integrated model of CDCA5 and FOXM1 expression combined with a residual disease that predicts prognosis in ovarian cancer patients.

机构信息

Department of Gynecological Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, China.

Bengbu Medical College,Bengbu, Anhui, 233004,China.

出版信息

Cell Mol Biol (Noisy-le-grand). 2023 Oct 31;69(10):143-149. doi: 10.14715/cmb/2023.69.10.20.

Abstract

Ovarian cancer (OC) is the most prevalent type of gynecologic cancer, leading to global death. Unfortunately, less than half of patients diagnosed with this cancer survive for up to five years. The factor forkhead box M1 (FOXM1) is a crucial oncoprotein in ovarian cancer and is currently recognized as a potential therapeutic target. The role of the Cell division cycle-associated 5 (CDCA5) is critical for advancing different types of cancers. However, the significance of CDCA5 in OC from a clinical perspective is not well comprehended. This study aimed to build a risk prognosis model and assess the data supporting the prognostic usefulness of CDCA5 and FOXM1 expression in patients with OC. In OC, we found that CDCA5 and FOXM1 were expressed. To establish the existence of variables that were independently related to PFS and OS, Cox regression, data from clinics, and Kaplan-Meier analysis were used. A risk score model and nomogram were created using the independent prognostic parameters. The accuracy of the model's predictions was then evaluated using decision curve analysis (DCA), calibration curve, and receiver operating characteristic(ROC) analysis. Finally, the patients were separated into groups based on their cut-off value, and then the differences in survival were investigated. Significant correlations were found between OC and CDCA5, and FOXM1 expression levels (P <0.0001). Serous ovarian tumors (P=0.025) and even specific subgroups of high-grade serous ovarian tumors were shown to have elevated CDCA5 expression levels. In our database, FOXM1 expression levels were discovered to be related to intestinal metastases (P=0.014). In OC, the expression of FOXM1 was positively correlated with the overexpression of CDCA5 (rs=0.46, P<0.0001). The results of the multivariate analysis indicated that residual disease (RD) (P=0.005), CDCA5 expression level (P=0.028), and FOXM1 expression level (P<0.0001) were identified as independent prognostic factors for PFS. Additionally, RD (P=0.023) and FOXM1 expression level (P<0.0001) were identified as independent prognostic factors for OS. While the prediction model's performance with RD was poor (AUC=0.645 for PFS, AUC=0.650 for OS), the model's performance with tissue biomarkers was enhanced (AUC=0.797 for PFS, AUC=0.741 for OS). The nomogram and risk score method showed a benefit for prognosis prediction. In summary, poor outcomes are predicted by CDCA5, which is overexpressed in OC patients and has a positive correlation with the level of FOXM1 expression. An aid to prognosis prediction in patients with OC and a resource for therapy planning is a risk prognosis model based on CDCA5 and FOXM1 expression with RD.

摘要

卵巢癌 (OC) 是最常见的妇科癌症类型,导致全球死亡。不幸的是,不到一半的被诊断出患有这种癌症的患者能存活五年以上。叉头框 M1 (FOXM1) 是卵巢癌中关键的癌蛋白,目前被认为是一个潜在的治疗靶点。细胞分裂周期相关蛋白 5 (CDCA5) 的作用对于推进不同类型的癌症至关重要。然而,从临床角度来看,CDCA5 在 OC 中的意义尚未被充分理解。本研究旨在构建风险预后模型,并评估支持 OC 患者 CDCA5 和 FOXM1 表达的预后有用性的数据。在 OC 中,我们发现 CDCA5 和 FOXM1 表达。为了建立与 PFS 和 OS 独立相关的变量的存在,使用 Cox 回归、临床数据和 Kaplan-Meier 分析。使用独立的预后参数创建风险评分模型和列线图。然后使用决策曲线分析 (DCA)、校准曲线和接收器工作特征 (ROC) 分析评估模型预测的准确性。最后,根据截断值将患者分为不同的组,然后研究生存差异。OC 与 CDCA5 和 FOXM1 表达水平之间存在显著相关性 (P<0.0001)。浆液性卵巢肿瘤 (P=0.025) 甚至高级别浆液性卵巢肿瘤的特定亚组显示出 CDCA5 表达水平升高。在我们的数据库中,FOXM1 表达水平与肠转移有关 (P=0.014)。在 OC 中,FOXM1 的表达与 CDCA5 的过表达呈正相关(rs=0.46, P<0.0001)。多变量分析的结果表明,残留疾病 (RD) (P=0.005)、CDCA5 表达水平 (P=0.028) 和 FOXM1 表达水平 (P<0.0001) 是 PFS 的独立预后因素。此外,RD (P=0.023) 和 FOXM1 表达水平 (P<0.0001) 是 OS 的独立预后因素。虽然基于 RD 的预测模型性能较差(AUC=0.645 用于 PFS,AUC=0.650 用于 OS),但组织生物标志物的模型性能得到了提高(AUC=0.797 用于 PFS,AUC=0.741 用于 OS)。列线图和风险评分方法显示出对预后预测的有益性。总之,OC 患者中 CDCA5 过表达,与 FOXM1 表达水平呈正相关,预示着预后不良。一种有助于 OC 患者预后预测和治疗计划的资源是基于 RD 的 CDCA5 和 FOXM1 表达的风险预后模型。

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