It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is ...It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still unclear.The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)dataset.Frequent HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC.HE4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways.The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects.Moreover,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD.Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.展开更多
目的:分析血清人附睾分泌蛋白4(Human epididymis protein 4,HE4)水平和子宫内膜癌患者临床病理特征的相关性.方法:回顾性分析2019年1月至2022年6月医院收治的120例子宫内膜癌患者临床资料.所有患者均实施子宫全切术治疗,收集患者的临...目的:分析血清人附睾分泌蛋白4(Human epididymis protein 4,HE4)水平和子宫内膜癌患者临床病理特征的相关性.方法:回顾性分析2019年1月至2022年6月医院收治的120例子宫内膜癌患者临床资料.所有患者均实施子宫全切术治疗,收集患者的临床病理特征资料,检测所有患者HE4水平,分析血清HE4水平与子宫内膜癌患者临床病理特征的相关性.结果:120例子宫内膜癌患者中,病理类型:子宫内膜样腺癌46例、子宫内膜样透明细胞癌36例、子宫内膜样鳞癌38例;淋巴结转移:发生35例、未发生85例;肌层浸润深度:>1/2肌层40例、≤1/2肌层80例;TNM分期:Ⅰ期22例、Ⅱ期43例、Ⅲ期55例.病灶所处部位:子宫底55例、子宫角37例、宫颈管28例.不同病理类型、TNM分期、病灶所处部位患者的血清HE4水平比较,差异无统计学意义;肌层浸润深度>1/2肌层患者的血清HE4水平高于肌层浸润深度≤1/2肌层的患者,发生淋巴结转移患者的血清HE4水平较未发生淋巴结转移的患者明显增加(P<0.05).经Logistic回归显示,血清HE4水平升高是子宫内膜癌患者肌层浸润深度>1/2肌层的风险因子(OR>1,P<0.05);血清HE4水平升高是子宫内膜癌患者发生淋巴结转移的风险因子(OR>1,P<0.05).结论:血清HE4水平升高增加可加剧肌层浸润深度,促使子宫内膜癌患者发生淋巴结转移.展开更多
Objective:To investigate the value of serum human epididymis protein 4(HE4) in differential diagnosis of patients with low-grade serous(LGSC) and high-grade serous carcinoma(HGSC) serous ovarian cancer.Methods:LGSC an...Objective:To investigate the value of serum human epididymis protein 4(HE4) in differential diagnosis of patients with low-grade serous(LGSC) and high-grade serous carcinoma(HGSC) serous ovarian cancer.Methods:LGSC and HGSC serous ovarian cancer were diagnosed by the two-tier grade system,serum levels of HE4 and carbohydrate antigen 12S(CA125) were measured by ELBA and radioisotope method,respectively in 60 serous ovarian cancer patients. HE4 and TPS3 protein in cancer tissue were measured by immunohistochemical method. Results:The difference in density of HE4 and TP53 protein was significant between LGSC and HGSC tissue,while serum CA12S did not show significant difference between different serum samples.There was significant difference in serum HE4 levels between LGSC and HGSC and the result was different within FIGO(Ⅰ+Ⅱ) stage,suggesting HE4 was not a reliable biomarker for the discrimination between LGSC and HCSC.HE4 had potential as a biomarker for the discrimination between LGSC and HGSC but the role in early diagnosis was limited.Conclusions:HE4 may be a reliable marker for differential diagnosis of LGSC and HGSC.But its role in early diagnosis of LGSC and HGSC need to be confirmed from the perspective of two-tier grade system.展开更多
基金supported by National Natural Science Foundation of China(82272695)the Key Program of Natural Science Foundation of Zhejiang Province(LZ23H160004)National Undergraduate Training Program for Innovation,and Zhejiang Xinmiao Talents Program,China.
文摘It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still unclear.The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)dataset.Frequent HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC.HE4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways.The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects.Moreover,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD.Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.
文摘目的:分析血清人附睾分泌蛋白4(Human epididymis protein 4,HE4)水平和子宫内膜癌患者临床病理特征的相关性.方法:回顾性分析2019年1月至2022年6月医院收治的120例子宫内膜癌患者临床资料.所有患者均实施子宫全切术治疗,收集患者的临床病理特征资料,检测所有患者HE4水平,分析血清HE4水平与子宫内膜癌患者临床病理特征的相关性.结果:120例子宫内膜癌患者中,病理类型:子宫内膜样腺癌46例、子宫内膜样透明细胞癌36例、子宫内膜样鳞癌38例;淋巴结转移:发生35例、未发生85例;肌层浸润深度:>1/2肌层40例、≤1/2肌层80例;TNM分期:Ⅰ期22例、Ⅱ期43例、Ⅲ期55例.病灶所处部位:子宫底55例、子宫角37例、宫颈管28例.不同病理类型、TNM分期、病灶所处部位患者的血清HE4水平比较,差异无统计学意义;肌层浸润深度>1/2肌层患者的血清HE4水平高于肌层浸润深度≤1/2肌层的患者,发生淋巴结转移患者的血清HE4水平较未发生淋巴结转移的患者明显增加(P<0.05).经Logistic回归显示,血清HE4水平升高是子宫内膜癌患者肌层浸润深度>1/2肌层的风险因子(OR>1,P<0.05);血清HE4水平升高是子宫内膜癌患者发生淋巴结转移的风险因子(OR>1,P<0.05).结论:血清HE4水平升高增加可加剧肌层浸润深度,促使子宫内膜癌患者发生淋巴结转移.
基金suuported by Young Researcher Foundation from Education Department of Jiangxi Province(Grand No.GJJ12161)
文摘Objective:To investigate the value of serum human epididymis protein 4(HE4) in differential diagnosis of patients with low-grade serous(LGSC) and high-grade serous carcinoma(HGSC) serous ovarian cancer.Methods:LGSC and HGSC serous ovarian cancer were diagnosed by the two-tier grade system,serum levels of HE4 and carbohydrate antigen 12S(CA125) were measured by ELBA and radioisotope method,respectively in 60 serous ovarian cancer patients. HE4 and TPS3 protein in cancer tissue were measured by immunohistochemical method. Results:The difference in density of HE4 and TP53 protein was significant between LGSC and HGSC tissue,while serum CA12S did not show significant difference between different serum samples.There was significant difference in serum HE4 levels between LGSC and HGSC and the result was different within FIGO(Ⅰ+Ⅱ) stage,suggesting HE4 was not a reliable biomarker for the discrimination between LGSC and HCSC.HE4 had potential as a biomarker for the discrimination between LGSC and HGSC but the role in early diagnosis was limited.Conclusions:HE4 may be a reliable marker for differential diagnosis of LGSC and HGSC.But its role in early diagnosis of LGSC and HGSC need to be confirmed from the perspective of two-tier grade system.
