Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protei...Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.展开更多
目的:探究卵巢-附件超声报告与数据系统(ovarian-adnexal reporting and data system ultrasonography,ORADS US)、计算机X线断层扫描(computed tomography,CT)和血清人附睾上皮分泌蛋白4(human epididymis protein 4,HE4)及这三者中任...目的:探究卵巢-附件超声报告与数据系统(ovarian-adnexal reporting and data system ultrasonography,ORADS US)、计算机X线断层扫描(computed tomography,CT)和血清人附睾上皮分泌蛋白4(human epididymis protein 4,HE4)及这三者中任意两者联合诊断(combined diagnosis,CD)对卵巢-附件肿瘤良恶性定性诊断的价值。方法:收集2021年1月至2024年1月宁夏医科大学总医院经病理确诊为卵巢-附件肿瘤患者的临床资料,术前均行US、CT及HE4检查,根据三种方法的诊断标准对患者进行定性诊断,分析O-RADS US、CT、HE4及CD方法对肿瘤良恶性的定性诊断。结果:311例患者中良性143例,恶性168例,CD的准确率为93.25%,敏感度为94.64%,特异度为91.61%,阳性预测值为92.98%,阴性预测值为93.57%,曲线下面积为0.985,均优于单一诊断,差异具有统计学意义(P<0.01)。结论:CD较单一诊断对卵巢-附件肿瘤良恶性的定性诊断具有明显的优势,提高了诊断的准确性,一定程度可避免单一诊断造成的漏诊及误诊。展开更多
目的探讨人血清CA125和人附睾蛋白4(human epididymis protein 4,HE4)水平在卵巢良恶性肿瘤鉴别诊断中的价值。方法测定187例女性血清标本,其中卵巢癌92例,卵巢良性疾病39例,健康体检女性56例,用微粒子酶免疫法(MEIA)和ELISA法分别测定...目的探讨人血清CA125和人附睾蛋白4(human epididymis protein 4,HE4)水平在卵巢良恶性肿瘤鉴别诊断中的价值。方法测定187例女性血清标本,其中卵巢癌92例,卵巢良性疾病39例,健康体检女性56例,用微粒子酶免疫法(MEIA)和ELISA法分别测定血清CA125和HE4含量。结果卵巢癌组CA125和HE4水平明显高于其他两组,差异有统计学意义(P<0.01)。健康对照组和良性疾病组HE4比较差异无统计学意义(P>0.05)。以卵巢良性疾病作参照,单独检测血清HE4水平对卵巢癌诊断的敏感性为57.6%,低于单独检测CA125的77.2%;但其特异性为97.0%,高于CA125的85.0%。以二者其中之一高于参考值即视为阳性时,联合检测HE4和CA125对卵巢癌诊断的敏感性为94.6%,特异性可达85.0%。结论联合检测血清CA125和HE4有助于卵巢良恶性肿瘤的诊断与鉴别诊断。展开更多
文摘Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.
文摘目的:探究卵巢-附件超声报告与数据系统(ovarian-adnexal reporting and data system ultrasonography,ORADS US)、计算机X线断层扫描(computed tomography,CT)和血清人附睾上皮分泌蛋白4(human epididymis protein 4,HE4)及这三者中任意两者联合诊断(combined diagnosis,CD)对卵巢-附件肿瘤良恶性定性诊断的价值。方法:收集2021年1月至2024年1月宁夏医科大学总医院经病理确诊为卵巢-附件肿瘤患者的临床资料,术前均行US、CT及HE4检查,根据三种方法的诊断标准对患者进行定性诊断,分析O-RADS US、CT、HE4及CD方法对肿瘤良恶性的定性诊断。结果:311例患者中良性143例,恶性168例,CD的准确率为93.25%,敏感度为94.64%,特异度为91.61%,阳性预测值为92.98%,阴性预测值为93.57%,曲线下面积为0.985,均优于单一诊断,差异具有统计学意义(P<0.01)。结论:CD较单一诊断对卵巢-附件肿瘤良恶性的定性诊断具有明显的优势,提高了诊断的准确性,一定程度可避免单一诊断造成的漏诊及误诊。
文摘目的探讨人血清CA125和人附睾蛋白4(human epididymis protein 4,HE4)水平在卵巢良恶性肿瘤鉴别诊断中的价值。方法测定187例女性血清标本,其中卵巢癌92例,卵巢良性疾病39例,健康体检女性56例,用微粒子酶免疫法(MEIA)和ELISA法分别测定血清CA125和HE4含量。结果卵巢癌组CA125和HE4水平明显高于其他两组,差异有统计学意义(P<0.01)。健康对照组和良性疾病组HE4比较差异无统计学意义(P>0.05)。以卵巢良性疾病作参照,单独检测血清HE4水平对卵巢癌诊断的敏感性为57.6%,低于单独检测CA125的77.2%;但其特异性为97.0%,高于CA125的85.0%。以二者其中之一高于参考值即视为阳性时,联合检测HE4和CA125对卵巢癌诊断的敏感性为94.6%,特异性可达85.0%。结论联合检测血清CA125和HE4有助于卵巢良恶性肿瘤的诊断与鉴别诊断。
