宫腔镜检查联合血清人附睾分泌蛋白及糖类抗原和miR-21早期诊断子宫内膜癌的临床价值
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摘要
目的探讨宫腔镜联合血清人附睾分泌蛋白(HE4)、糖类抗原(CA-125)、miR-21检测在子宫内膜癌早期诊断中的临床价值。方法选择2016年1月至2017年11月郑州市第二人民医院收治的早期子宫内膜癌患者75例为子宫内膜癌组,另以同期收治的70例子宫内膜增生患者为子宫内膜增生组,同期70例体检健康者为健康对照组,比较各组受试者血清HE4、CA-125、miR-21水平及其与子宫内膜癌临床病理特征的关系;以病理检查结果为金标准,评估宫腔镜检查和血清HE4、CA-125、miR-21单独及联合检测对早期子宫内膜癌的诊断价值。结果 3组受试者血清HE4、CA-125、miR-21水平比较差异均有统计学意义(F=329. 520、267. 532、226. 882,P <0. 05)。子宫内膜增生组和子宫内膜癌组患者血清HE4、CA-125、miR-21水平显著高于健康对照组(P <0. 05)。子宫内膜癌组患者血清HE4、CA-125、miR-21水平显著高于子宫内膜增生组(P <0. 05)。早期子宫内膜癌患者组织分级、肌层浸润与HE4、CA-125、miR-21水平具有相关性(P <0. 05)。多因素logistic回归分析显示,早期子宫内膜癌的发生与HE4、CA-125、miR-21均密切相关(OR=1. 456、1. 662、2. 507,P <0. 05)。以HE4> 70. 45 pmol·L-1、CA-125> 31. 05×103U·L-1、miR-21> 1. 28作为阳性判定标准,miR-21、宫腔镜单独诊断早期子宫内膜癌的灵敏度和准确度显著高于HE4和CA-125(P <0. 05)。宫腔镜+HE4+miR-21联合诊断早期子宫内膜癌的灵敏度显著高于miR-21(P <0. 05)。HE4+CA-125+miR-21、宫腔镜+HE4+CA-125、宫腔镜+CA-125+miR-21、宫腔镜+HE4+miR-21及宫腔镜+HE4+CA-125+miR-21联合诊断早期子宫内膜癌的灵敏度和准确度显著高于血清HE4、CA-125(P <0. 05),宫腔镜+HE4+CA-125+miR-21联合诊断早期子宫内膜癌的灵敏度显著高于宫腔镜检查(P <0. 05)。结论宫腔镜检查与血清学指标HE4、CA-125、miR-21联合诊断子宫内膜癌的价值高于各项单独诊断的价值;宫腔镜联合其中2种血清学指标的诊断效能与宫腔镜同时联合3种血清学指标的诊断效能相似,因此可以考虑选择最佳的血清学指标与宫腔镜联合进行诊断。
Objective To investigate the clinical value of hysteroscopy combined with serum human epididymal protein( HE4),carbohydrate antigen 125( CA-125) and miR-21 in the early diagnosis of endometrial carcinoma. Methods Seventyfive patients with early endometrial carcinoma in Zhengzhou Second Hospital from January 2016 to November 2017 were selected as endometrial carcinoma group,seventy patients with endometrial hyperplasia were selected as endometrial hyperplasia group,and seventy healthy people were selected as the healthy control group in the same period. The serum levels of HE4,CA-125 and microRNA-21 were compared among the groups,and the relationship between the levels of serum HE4,CA-125 and microRNA-21 and clinicopathological features of endometrial carcinoma was analyzed. The value of hysteroscopy and serum HE4,CA-125 and miR-21 in the early diagnosis of endometrial carcinoma was evaluated according to the results of pathological examination. Results There were significant difference in the levels of HE4,CA-125 and miR-21 among the three groups( F = 329. 520,267. 532,226. 882; P < 0. 05). The levels of HE4,CA-125 and miR-21 in endometrial hyperplasia group and endometrial carcinoma group were significantly higher than those in healthy control group( P < 0. 05). The levels of HE4,CA-125 and miR-21 in endometrial carcinoma group were significantly higher than those in endometrial hyperplasia group( P < 0. 05). The levels of serum HE4,CA-125 and miR-21 were correlated with histological grade and myometrial infiltration in patients with endometrial carcinoma( P < 0. 05). The multivariate logistic regression analysis showed that the occurrence of endometrial carcinoma was closely related to HE4,CA-125 and miR-21( OR = 1. 456,1. 662,2. 507; P < 0. 05). With HE4 >70. 45 pmol·L-1,CA-125 > 31. 05 × 103 U·L-1 and miR-21 > 1. 28 as the positive criteria,the sensitivity and accuracy of the separate detection of miR-21 or hysteroscopy in the diagnosis of early endometrial carcinoma were significantly higher than those of the separate detection of HE4 or CA-125( P < 0. 05). The sensitivity of the combined detection of hysteroscopy +HE4 + miR-21 were significantly higher than that of the separate detection of miR-21 in the diagnosis of early endometrial carcinoma( P < 0. 05). The sensitivity and accuracy of the combined detection of HE4 + CA-125 + miR-21,hysteroscopy +HE4 + CA-125,hysteroscopy + CA-125 + miR-21,hysteroscopy + HE4 + miR-21 or hysteroscopy + HE4 + CA-125 + miR-21 were significantly higher than those of the separate detection of HE4 or CA-125 in the diagnosis of early endometrial carcinoma( P < 0. 05). The sensitivity of the combined detection of hysteroscopy + HE4 + CA-125 + miR-21 was significantly higher than that of hysteroscopy in the diagnosis of early endometrial carcinoma( P < 0. 05). Conclusion The value of the combined detection of hysteroscopy,HE4,CA-125 and miR-21 is higher than that of the separate detection of them in the diagnosis of endometrial carcinoma. The diagnostic efficacy of hysteroscopy combined with two serological indicators is similar to that of hysteroscopy combined with three serological indicators. Therefore,the combined detection of the best serological indicators and hysteroscopy can be selected for the diagnosis of early endometrial carcinoma.
Objective To investigate the clinical value of hysteroscopy combined with serum human epididymal protein( HE4),carbohydrate antigen 125( CA-125) and miR-21 in the early diagnosis of endometrial carcinoma. Methods Seventyfive patients with early endometrial carcinoma in Zhengzhou Second Hospital from January 2016 to November 2017 were selected as endometrial carcinoma group,seventy patients with endometrial hyperplasia were selected as endometrial hyperplasia group,and seventy healthy people were selected as the healthy control group in the same period. The serum levels of HE4,CA-125 and microRNA-21 were compared among the groups,and the relationship between the levels of serum HE4,CA-125 and microRNA-21 and clinicopathological features of endometrial carcinoma was analyzed. The value of hysteroscopy and serum HE4,CA-125 and miR-21 in the early diagnosis of endometrial carcinoma was evaluated according to the results of pathological examination. Results There were significant difference in the levels of HE4,CA-125 and miR-21 among the three groups( F = 329. 520,267. 532,226. 882; P < 0. 05). The levels of HE4,CA-125 and miR-21 in endometrial hyperplasia group and endometrial carcinoma group were significantly higher than those in healthy control group( P < 0. 05). The levels of HE4,CA-125 and miR-21 in endometrial carcinoma group were significantly higher than those in endometrial hyperplasia group( P < 0. 05). The levels of serum HE4,CA-125 and miR-21 were correlated with histological grade and myometrial infiltration in patients with endometrial carcinoma( P < 0. 05). The multivariate logistic regression analysis showed that the occurrence of endometrial carcinoma was closely related to HE4,CA-125 and miR-21( OR = 1. 456,1. 662,2. 507; P < 0. 05). With HE4 >70. 45 pmol·L-1,CA-125 > 31. 05 × 103 U·L-1 and miR-21 > 1. 28 as the positive criteria,the sensitivity and accuracy of the separate detection of miR-21 or hysteroscopy in the diagnosis of early endometrial carcinoma were significantly higher than those of the separate detection of HE4 or CA-125( P < 0. 05). The sensitivity of the combined detection of hysteroscopy +HE4 + miR-21 were significantly higher than that of the separate detection of miR-21 in the diagnosis of early endometrial carcinoma( P < 0. 05). The sensitivity and accuracy of the combined detection of HE4 + CA-125 + miR-21,hysteroscopy +HE4 + CA-125,hysteroscopy + CA-125 + miR-21,hysteroscopy + HE4 + miR-21 or hysteroscopy + HE4 + CA-125 + miR-21 were significantly higher than those of the separate detection of HE4 or CA-125 in the diagnosis of early endometrial carcinoma( P < 0. 05). The sensitivity of the combined detection of hysteroscopy + HE4 + CA-125 + miR-21 was significantly higher than that of hysteroscopy in the diagnosis of early endometrial carcinoma( P < 0. 05). Conclusion The value of the combined detection of hysteroscopy,HE4,CA-125 and miR-21 is higher than that of the separate detection of them in the diagnosis of endometrial carcinoma. The diagnostic efficacy of hysteroscopy combined with two serological indicators is similar to that of hysteroscopy combined with three serological indicators. Therefore,the combined detection of the best serological indicators and hysteroscopy can be selected for the diagnosis of early endometrial carcinoma.
引文
[1]杨曦,马珂,吴成.子宫内膜癌的流行病学及高危因素[J].实用妇产科杂志,2015,31(7):485-488.
[2]李小毛,杨晓辉,杨越波,等.宫腔镜辅助分段诊刮术在子宫内膜癌诊断中的价值[J].中华妇产科杂志,2015,50(2):120-124.
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[4]朱春霞,孟勇,王秀虹.血清人附睾分泌蛋白4、糖类抗原125和脂联素在子宫内膜癌淋巴结转移诊断中的价值[J].新乡医学院学报,2016,33(5):403-405+410.
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[6]沈铿,彭澎,吴鸣.国际妇产科联盟妇科肿瘤2009年分期的解读[J].中华妇产科杂志,2010,45(10):721-724.
[7]刘艳林.宫腔镜检查在子宫内膜癌及癌前病变筛查中的应用价值[J].临床和实验医学杂志,2015,14(14):1215-1218.
[8] GKROZOU F,DIMAKOPOULOS G,VREKOUSSIS T,et al.Hysteroscopy in women with abnormal uterine bleeding:a metaanalysis on four major endometrial pathologies[J]. Arch Gynecol Obstet,2015,291(6):1347-1354.
[9] ABDALLA N,PIRKOWSKI R,STANIROWSKI P,et al. Assessment of levels of the tumor markers HE4 and CA125 considering staging,grading and histological types of endometrial cancer[J].Prz Menopauzalny,2016,15(3):133-137.
[10] ABBINK K,ZUSTERZEEL P L,GEURTS-MOESPOT A J,et al.HE4 is superior to CA125 in the detection of recurrent disease in high-risk endometrial cancer patients[J]. Tumour Biol,2018,40(2):1-10.
[11] BIAN J,SUN X,LI B,et al. Clinical significance of serum HE4,CA125,CA724,and CA19-9 in patients with endometrial cancer[J]. Technol Cancer Res Treat,2017,16(4):435-439.
[12]陈安霞,滕飞,王颖梅,等.血清HE4、CA125联合检测对Ⅰ期高危子宫内膜癌患者的预测价值[J].天津医药,2016,44(6):729-732.
[13] PERALTA-ZARAGOZA O,DEAS J,MENESES-ACOSTA A,et al. Relevance of mir-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells[J]. BMC Cancer,2016,16(1):215.
[14] PARK Y S,LEE J H,JUNG D B,et al. MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma[J]. Sci Rep,2018,8(1):17717.
[15] GAO Y,DAI M,LIU H,et al. Diagnostic value of circulating miR-21:an update meta-analysis in various cancers and validation in endometrial cancer[J]. Oncotarget,2016,7(42):68894-68908.
[16]项锦红,丁秋霞,黄强,等.沉默miR-21对子宫内膜癌顺铂耐药细胞株Ishikawa/DDP的影响[J].临床与病理杂志,2017,37(5):925-931.
[2]李小毛,杨晓辉,杨越波,等.宫腔镜辅助分段诊刮术在子宫内膜癌诊断中的价值[J].中华妇产科杂志,2015,50(2):120-124.
[3]艾永航.宫腔镜在子宫内膜癌诊断中的应用价值[J].中华妇幼临床医学杂志:电子版,2015,11(1):69-71. DOI:10. 3877/cma. j. issn. 1673-5250. 2015. 01. 016.
[4]朱春霞,孟勇,王秀虹.血清人附睾分泌蛋白4、糖类抗原125和脂联素在子宫内膜癌淋巴结转移诊断中的价值[J].新乡医学院学报,2016,33(5):403-405+410.
[5] CHEN Y,REN Y L,LI N,et al. Serum human epididymis protein 4vs. carbohydrate antigen 125 and their combination for endometrial cancer diagnosis:a meta-analysis[J]. Eur Rev Med Pharmacol Sci,2016,20(10):1974-1985.
[6]沈铿,彭澎,吴鸣.国际妇产科联盟妇科肿瘤2009年分期的解读[J].中华妇产科杂志,2010,45(10):721-724.
[7]刘艳林.宫腔镜检查在子宫内膜癌及癌前病变筛查中的应用价值[J].临床和实验医学杂志,2015,14(14):1215-1218.
[8] GKROZOU F,DIMAKOPOULOS G,VREKOUSSIS T,et al.Hysteroscopy in women with abnormal uterine bleeding:a metaanalysis on four major endometrial pathologies[J]. Arch Gynecol Obstet,2015,291(6):1347-1354.
[9] ABDALLA N,PIRKOWSKI R,STANIROWSKI P,et al. Assessment of levels of the tumor markers HE4 and CA125 considering staging,grading and histological types of endometrial cancer[J].Prz Menopauzalny,2016,15(3):133-137.
[10] ABBINK K,ZUSTERZEEL P L,GEURTS-MOESPOT A J,et al.HE4 is superior to CA125 in the detection of recurrent disease in high-risk endometrial cancer patients[J]. Tumour Biol,2018,40(2):1-10.
[11] BIAN J,SUN X,LI B,et al. Clinical significance of serum HE4,CA125,CA724,and CA19-9 in patients with endometrial cancer[J]. Technol Cancer Res Treat,2017,16(4):435-439.
[12]陈安霞,滕飞,王颖梅,等.血清HE4、CA125联合检测对Ⅰ期高危子宫内膜癌患者的预测价值[J].天津医药,2016,44(6):729-732.
[13] PERALTA-ZARAGOZA O,DEAS J,MENESES-ACOSTA A,et al. Relevance of mir-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells[J]. BMC Cancer,2016,16(1):215.
[14] PARK Y S,LEE J H,JUNG D B,et al. MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma[J]. Sci Rep,2018,8(1):17717.
[15] GAO Y,DAI M,LIU H,et al. Diagnostic value of circulating miR-21:an update meta-analysis in various cancers and validation in endometrial cancer[J]. Oncotarget,2016,7(42):68894-68908.
[16]项锦红,丁秋霞,黄强,等.沉默miR-21对子宫内膜癌顺铂耐药细胞株Ishikawa/DDP的影响[J].临床与病理杂志,2017,37(5):925-931.