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Abstract：
BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a rare pathological histotype in ovarian cancer, while the survival rate of advanced OCCC (Stage III-IV) is substantially lower than that of the advanced serous ovarian cancer (OSC), which is the most common histotype. The goal of this study was to identify high-risk OCCC by comparing OSC and OCCC, with investigating potential risk and prognosis markers.
METHODS: Patients diagnosed with ovarian cancer from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Logistic and Cox regression models were used to identify risk and prognostic factors in high-risk OCCC patients. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier curves. Furthermore, Cox analysis was employed to build a nomogram model. The performance evaluation results were displayed using the C-index, calibration plots, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Immunohistochemically approach was used to identify the expression of the novel target (GPC3).
RESULTS: In the Cox analysis for advanced OCCC, age (45-65 years), tumor numbers (total number of in situ/malignant tumors for patient), T3-stage, bilateral tumors, and liver metastases could be defined as prognostic variables. Nomogram showed good predictive power and clinical practicality. Compared with OSC, liver metastases had a stronger impact on the prognosis of patients with OCCC. T3-stage, positive distant lymph nodes metastases, and lung metastases were risk factors for developing liver metastases. Chemotherapy was an independent prognostic factor for patient with advanced OCCC, but had no effect on CSS in patients with liver metastases (p = 0.0656), while surgery was significantly related with better CSS in these patients (p < 0.0001) (p = 0.0041). GPC3 expression was detected in all tissue sections, and GPC3 staining was predominantly found in the cytoplasm and membranes.
CONCLUSIONS: Advanced OCCC and OCCC with liver metastases are two types of high-risk OCCC. The constructed nomogram exhibited a satisfactory survival prediction for patients with advanced OCCC. GPC3 immunohistochemistry is expected to accumulate preclinical evidence to support the inclusion of GPC3 in OCCC targeted therapy.
METHODS: Patients diagnosed with ovarian cancer from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Logistic and Cox regression models were used to identify risk and prognostic factors in high-risk OCCC patients. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier curves. Furthermore, Cox analysis was employed to build a nomogram model. The performance evaluation results were displayed using the C-index, calibration plots, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Immunohistochemically approach was used to identify the expression of the novel target (GPC3).
RESULTS: In the Cox analysis for advanced OCCC, age (45-65 years), tumor numbers (total number of in situ/malignant tumors for patient), T3-stage, bilateral tumors, and liver metastases could be defined as prognostic variables. Nomogram showed good predictive power and clinical practicality. Compared with OSC, liver metastases had a stronger impact on the prognosis of patients with OCCC. T3-stage, positive distant lymph nodes metastases, and lung metastases were risk factors for developing liver metastases. Chemotherapy was an independent prognostic factor for patient with advanced OCCC, but had no effect on CSS in patients with liver metastases (p = 0.0656), while surgery was significantly related with better CSS in these patients (p < 0.0001) (p = 0.0041). GPC3 expression was detected in all tissue sections, and GPC3 staining was predominantly found in the cytoplasm and membranes.
CONCLUSIONS: Advanced OCCC and OCCC with liver metastases are two types of high-risk OCCC. The constructed nomogram exhibited a satisfactory survival prediction for patients with advanced OCCC. GPC3 immunohistochemistry is expected to accumulate preclinical evidence to support the inclusion of GPC3 in OCCC targeted therapy.
摘要：
背景：卵巢透明细胞癌（OCCC）是一种罕见的卵巢癌病理组织学类型，尽管晚期OCCC（III-IV期）的生存率大大低于晚期浆液性卵巢癌（OSC），这是最常见的组织型。这项研究的目的是通过比较OSC和OCCC来识别高风险的OCCC，调查潜在的风险和预后标志物。
方法：从监测中确定了2009年至2018年诊断为卵巢癌的患者，流行病学,和最终结果（SEER）计划。使用Logistic和Cox回归模型来确定高危OCCC患者的风险和预后因素。使用Kaplan-Meier曲线评估癌症特异性存活(CSS)和总存活(OS)。此外，采用Cox分析建立列线图模型。使用C指数显示性能评估结果，校准图,接收机工作特性(ROC)曲线,和决策曲线分析(DCA)。免疫组织化学方法用于鉴定新靶标(GPC3)的表达。
结果：在高级OCCC的Cox分析中，年龄（45-65岁），肿瘤数量（患者的原位/恶性肿瘤总数），T3阶段，双侧肿瘤，肝转移可以定义为预后变量。列线图显示出良好的预测能力和临床实用性。与OSC相比,肝转移对OCCC患者的预后有更强的影响.T3阶段，远处淋巴结转移阳性，肺转移是肝转移的危险因素。化疗是晚期OCCC患者的独立预后因素。但对肝转移患者的CSS没有影响（p=0.0656），而在这些患者中，手术与更好的CSS显着相关（p<0.0001）（p=0.0041）。在所有组织切片中检测到GPC3表达，GPC3染色主要见于细胞质和细胞膜。
结论：晚期OCCC和有肝转移的OCCC是两种高危OCCC。构建的列线图对晚期OCCC患者表现出令人满意的生存预测。GPC3免疫组织化学有望积累临床前证据，以支持将GPC3纳入OCCC靶向治疗。
方法：从监测中确定了2009年至2018年诊断为卵巢癌的患者，流行病学,和最终结果（SEER）计划。使用Logistic和Cox回归模型来确定高危OCCC患者的风险和预后因素。使用Kaplan-Meier曲线评估癌症特异性存活(CSS)和总存活(OS)。此外，采用Cox分析建立列线图模型。使用C指数显示性能评估结果，校准图,接收机工作特性(ROC)曲线,和决策曲线分析(DCA)。免疫组织化学方法用于鉴定新靶标(GPC3)的表达。
结果：在高级OCCC的Cox分析中，年龄（45-65岁），肿瘤数量（患者的原位/恶性肿瘤总数），T3阶段，双侧肿瘤，肝转移可以定义为预后变量。列线图显示出良好的预测能力和临床实用性。与OSC相比,肝转移对OCCC患者的预后有更强的影响.T3阶段，远处淋巴结转移阳性，肺转移是肝转移的危险因素。化疗是晚期OCCC患者的独立预后因素。但对肝转移患者的CSS没有影响（p=0.0656），而在这些患者中，手术与更好的CSS显着相关（p<0.0001）（p=0.0041）。在所有组织切片中检测到GPC3表达，GPC3染色主要见于细胞质和细胞膜。
结论：晚期OCCC和有肝转移的OCCC是两种高危OCCC。构建的列线图对晚期OCCC患者表现出令人满意的生存预测。GPC3免疫组织化学有望积累临床前证据，以支持将GPC3纳入OCCC靶向治疗。
