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:探讨血清人附睾上皮分泌蛋白4(human epididymis protein 4,HE4)和CA125联合检测在卵巢癌诊断中的应用价值。方法:采用ELISA法检测35例卵巢癌患者、60例卵巢良性疾病患者及66例健康对照者血清HE4水平,同时采用化学发光法检测血清CA...目的:探讨血清人附睾上皮分泌蛋白4(human epididymis protein 4,HE4)和CA125联合检测在卵巢癌诊断中的应用价值。方法:采用ELISA法检测35例卵巢癌患者、60例卵巢良性疾病患者及66例健康对照者血清HE4水平,同时采用化学发光法检测血清CA125水平,分析两标志物单项或联合检测对卵巢癌的诊断价值。结果:卵巢癌患者血清HE4和CA125水平均明显高于卵巢良性疾病患者和健康对照者(P均<0.01)。血清HE4和CA125联合检测对卵巢癌诊断的敏感性均高于两者单项检测,为82.9%,其特异性高于CA125单项检测,低于HE4单项检测。在卵巢癌早期诊断中,血清HE4单项检测的敏感性高于CA125单项检测。结论:血清HE4和CA125联合检测可以提高卵巢癌的诊断能力。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:探讨血清人附睾上皮分泌蛋白4(human epididymis protein 4,HE4)和CA125联合检测在卵巢癌诊断中的应用价值。方法:采用ELISA法检测35例卵巢癌患者、60例卵巢良性疾病患者及66例健康对照者血清HE4水平,同时采用化学发光法检测血清CA125水平,分析两标志物单项或联合检测对卵巢癌的诊断价值。结果:卵巢癌患者血清HE4和CA125水平均明显高于卵巢良性疾病患者和健康对照者(P均<0.01)。血清HE4和CA125联合检测对卵巢癌诊断的敏感性均高于两者单项检测,为82.9%,其特异性高于CA125单项检测,低于HE4单项检测。在卵巢癌早期诊断中,血清HE4单项检测的敏感性高于CA125单项检测。结论:血清HE4和CA125联合检测可以提高卵巢癌的诊断能力。
