宫颈癌患者血清hsa-miR-200a-3p的表达及其意义
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摘要
目的探讨宫颈癌患者血清hsa-miR-200a-3p的表达水平及其对宫颈癌的辅助诊断价值。方法收集55例宫颈癌患者、32例宫颈上皮内瘤变(CIN)患者、39例子宫肌瘤患者及47例健康对照者血清样本,分别测定hsa-miR-200a-3p的表达水平及糖链抗原125(CA125)和人鳞状细胞癌相关抗原(SCCAg)水平。分析血清hsa-miR-200a-3p的表达水平与临床病理特征、CA125和SCCAg之间的关系。用受试者工作特征曲线(ROC曲线)评价3项指标单独及联合检测对宫颈癌的辅助诊断价值。结果宫颈癌患者血清hsa-miR-200a-3p的相对表达量均高于子宫肌瘤患者和健康对照者,差异有统计学意义(P<0.001)。CIN患者血清hsa-miR-200a-3p的相对表达量均高于子宫肌瘤患者和健康对照者,差异有统计学意义(P<0.05)。子宫肌瘤患者和健康对照者血清hsa-miR-200a-3p的相对表达量差异无统计学意义(P>0.05)。宫颈癌患者血清hsa-miR-200a-3p的表达水平在年龄大小、是否绝经、肿瘤最大直径、FIGO分期间差异均无统计学意义(P>0.05),宫颈癌患者血清hsa-miR-200a-3p相对表达量与CA125(r2=0.012,P=0.421)、SCCAg(r2=0.004,P=0.647)无相关性。ROC曲线分析血清has-miR-200a-3p检测对宫颈癌患者的辅助诊断价值,宫颈癌区分于子宫肌瘤时,ROC曲线下面积(AUC)为0.753;宫颈癌患者区分于健康对照者时,AUC为0.771。结论宫颈癌患者血清hsamiR-200a-3p相对表达量高于子宫肌瘤组和健康对照组,有可能成为宫颈癌辅助诊断的重要生物学指标。血清hsa-miR-200a-3p的表达水平或可用于CIN的辅助诊断。
Objective To explore the level of serum hsa-miR-200 a-3 p in cervical cancer patients and its diagnostic value in cervical cancer.Methods Serum samples of 55 patients with cervical cancer,32 patients with cervical intraepithelial neoplasia(CIN),39 cases of uterine fibroids and 47 healthy controls were collected.The levels of hsa-miR-200 a-3 p,sugar chain antigen 125(CA125)and human squamous cell carcinoma associated antigen(SCCAg)were determined respectively.The relationship between the level of serum hsa-mir-200 a-3 p and clinicopathological features,CA125 and SCCAAg levels was analyzed.ROC curve was used to evaluate the diagnostic value of single and combined detection of hsa-miR-200 a-3 p,CA125 and SCCAg.Results The relative expression of serum hsa-miR-200 a-3 p in patients with cervical cancer was higher than that in patients with uterine leiomyoma and healthy controls,and the difference was statistically significant(P<0.001).The relative expression of serum hsa-miR-200 a-3 p in patients with CIN was higher than that in patients with uterine leiomyoma and healthy controls,and the difference was statistically significant(P<0.05).There was no significant difference between relative expression of serum hsa-miR-200 a-3 p in patients with uterine fibroids and healthy controls(P>0.05).There was no significant difference in the expression level of hsa-miR-200 a-3 p between age,menopause,maximum tumor diameter and FIGO stage in cervical cancer patients(P>0.05).The relative expression of hsa-miR-200 a-3 p was not correlated with CA125(r2=0.012,P=0.421),SCCAg(r2=0.004,P=0.647).When cervical cancer was distinguished from uterine fibroids,area under receiver operating characteristic(ROC)Curve(AUC)was 0.753,the AUC was 0.771 when cervical cancer was distinguished from healthy control.Conclusion Serum hsa-miR-200 a-3 p expression was higher in cervical cancer patients than those in the uterine fibroids group and healthy control group,and it could be an important biological indicator for cervical cancer adjuvant diagnosis.At the same time,the expression of serum hsa-miR-200 a-3 p may be used for the auxiliary diagnosis of CIN.
Objective To explore the level of serum hsa-miR-200 a-3 p in cervical cancer patients and its diagnostic value in cervical cancer.Methods Serum samples of 55 patients with cervical cancer,32 patients with cervical intraepithelial neoplasia(CIN),39 cases of uterine fibroids and 47 healthy controls were collected.The levels of hsa-miR-200 a-3 p,sugar chain antigen 125(CA125)and human squamous cell carcinoma associated antigen(SCCAg)were determined respectively.The relationship between the level of serum hsa-mir-200 a-3 p and clinicopathological features,CA125 and SCCAAg levels was analyzed.ROC curve was used to evaluate the diagnostic value of single and combined detection of hsa-miR-200 a-3 p,CA125 and SCCAg.Results The relative expression of serum hsa-miR-200 a-3 p in patients with cervical cancer was higher than that in patients with uterine leiomyoma and healthy controls,and the difference was statistically significant(P<0.001).The relative expression of serum hsa-miR-200 a-3 p in patients with CIN was higher than that in patients with uterine leiomyoma and healthy controls,and the difference was statistically significant(P<0.05).There was no significant difference between relative expression of serum hsa-miR-200 a-3 p in patients with uterine fibroids and healthy controls(P>0.05).There was no significant difference in the expression level of hsa-miR-200 a-3 p between age,menopause,maximum tumor diameter and FIGO stage in cervical cancer patients(P>0.05).The relative expression of hsa-miR-200 a-3 p was not correlated with CA125(r2=0.012,P=0.421),SCCAg(r2=0.004,P=0.647).When cervical cancer was distinguished from uterine fibroids,area under receiver operating characteristic(ROC)Curve(AUC)was 0.753,the AUC was 0.771 when cervical cancer was distinguished from healthy control.Conclusion Serum hsa-miR-200 a-3 p expression was higher in cervical cancer patients than those in the uterine fibroids group and healthy control group,and it could be an important biological indicator for cervical cancer adjuvant diagnosis.At the same time,the expression of serum hsa-miR-200 a-3 p may be used for the auxiliary diagnosis of CIN.
引文
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[15]XU F,HE H,HUANG W,et al.Decread expression of MiRNA-200family in human breast cancer is associated with lymph node metastasis[J].Clin Transl Oncol,2015,25(2):32-39.
[16]DA SILVA C L,BROHEM C A,CORRA T C,et al.Higher expression and activity of metalloproteinases in human cervical carcinoma cell lines is associated with HPV presence[J].Biochem Cell Biol,2006,84(5):713-739.
[2] DUENAS-GONZALEZ A,SERRANO-OLVERA A,CETINA L,et al.New molecular targets against cervical cancer[J].Int J Womens Health,2014,6(4):1023-1031.
[3] KASINSKI A L S F,genetics.MicroRNAs en route to the clinic:progress in validating and targeting microRNAs for cancer therapy[J].Nat Rev Cancer,2011,11(12):849-864.
[4] SHI T Y,CHENG X,YU K D,et al.Functional variants in TNFAIP8associated with cervical cancer susceptibility and clinical outcomes[J].Carcinogenesis,2013,34(4):770-778.
[5] XU Y Q,GU L,PAN Y Q,et al.Different effects of three polymorphisms in MicroRNAs on cancer risk in Asian population:evidence from published literatures[J].PLoS One,2013,8(6):e65123.
[6] SILVA S S,LOPES C,TEIXEIRA A L,et al.Forensic miRNA:potential biomarker for body fluids?[J].Forensic Sci Int Genet,2015,1(14):1-10.
[7] KOEBERLE V,PLELI T,SCHMITHALS C,et al.Differential stability of Cell-Free circulating microRNAs:implications for their utilization as biomarkers[J].PLoS One,2013,8(9):e75184-e75194.
[8]刘锋,王占祥,黄才权,等.miR-200a通过靶向NCAM1基因影响胶质瘤细胞的迁移及侵袭[J].肿瘤,2013,33(5):398-403.
[9]张占薪,罗大虎,崔金全.has-miRNA-200b在宫颈癌中的表达及意义[J].中国实用妇科与产科杂志,2010,26(5):386-387.
[10]GONZLEZ-QUINTANAV,PALMA-BERRL,CAMPOS-PARRA AD,etal.MicroRNAs are involvedin cervicalcancer development,progression,clinical outcome and improvementtreatmentresponse(Review)[J].Oncol Rep,2016,35(1):3-12.
[11]XIA H,NG S S,JIANG S,et al.miR-200a-mediated downregulation of ZEB2and CTNNB1differentially inhibits nasopharyngeal carcinoma cell growth,migration and invasion[J].Biochem Biophys Res Commun,2010,391(1):535-541.
[12]WU Q,GUO R,LIN M,et al.MicorRNA-200ainhibits CD133/1+ovarian cancer stem cells migration and invasion by targeting E-cadherin repressor ZEB2[J].Gynecol Oncol,2011,122(1):149-154.
[13]YEUNG C L A,TSANG T Y,YAU P L,et al.Human papillomavirus type 16E6induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway[J].Oncogene,2011,30(21):2401-2410.
[14]CAO Q,LU K L,DAI S P,et al.Clinicopathological and prognostic implications of the miR-200family in patients with epithelial ovarian cancer[J].Int J Clin Exp Pathol,2014,7(5):2392-2401.
[15]XU F,HE H,HUANG W,et al.Decread expression of MiRNA-200family in human breast cancer is associated with lymph node metastasis[J].Clin Transl Oncol,2015,25(2):32-39.
[16]DA SILVA C L,BROHEM C A,CORRA T C,et al.Higher expression and activity of metalloproteinases in human cervical carcinoma cell lines is associated with HPV presence[J].Biochem Cell Biol,2006,84(5):713-739.