血清microRNA-4286表达与胃癌临床病理特征的关系及其临床意义
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摘要
目的探讨胃癌患者血清microRNA-4286(miR-4286)的表达水平与胃癌临床病理特征的关系,分析其对胃癌的临床诊断效能及意义。方法通过实时荧光定量聚合酶链反应检测健康体检者(对照组)和胃癌患者(胃癌组)血清miR-4286的表达,分析miR-4286的表达量与胃癌临床病理特征的关系;通过受试者工作特征曲线和危险分数分析法评估miR-4286对胃癌的诊断效能;通过电化学发光免疫分析法检测血清肿瘤标志物CEA、CA19-9和CA72-4的表达。结果胃癌组患者血清中miR-4286表达量高于对照祖(P<0.05)。miR-4286的表达水平与胃癌患者的临床分期、淋巴结转移及远处转移等无关(P>0.05),与肿瘤细胞分化程度有关(P <0.05)。两组血清中CEA、CA19-9表达量比较,差异无统计学意义(P>0.05),胃癌组CA72-4表达量较对照组升高(P<0.05)。miR-4286诊断胃癌的曲线下面积为0.727,特异性和阳性预测值分别为90%和0.872,高于肿瘤标志物CA72-4。结论 miR-4286在胃癌血清中高表达,其表达水平与病理分化程度有关,可能成为胃癌临床诊断的潜在指标。
Objective To investigate the correlation between the expression level of serum miR-4286 and clinicopathological characteristics of gastric cancer, and analyze its efficacy and significance in clinical diagnosis of gastric cancer. Methods Real time fluorescence quantitative PCR was used to detect the expression of miR-4286 in serum samples of healthy control group and gastric cancer group. The correlation between the expression of miR-4286 and the clinicopathological features of gastric cancer was analyzed by statistical methods; Diagnostic efficacy of miR-4286 for gastric cancer was assessed by receiver operating characteristic curve and risk score analysis; Expression of tumor markers CEA, CA19-9, and CA72-4 were detected by electrochemiluminescence immunoassay. Results The expression of miR-4286 in the serum of gastric cancer group was higher than that in healthy control group(Z =-4.644,P < 0.0001). The expression level of miR-4286 in gastric cancer group was not related to tumor clinical stage, lymph node metastasis and distant metastasis(P > 0.05), but it was negatively correlated with the degree of pathological differentiation of tumor cells(Z =-2.661, P < 0.01). Compared with the control group, there was no significant difference in the expression of CEA and CA19-9 in the serum of gastric cancer group(P > 0.05), but the expression of CA72-4 was increased(Z =-3.324, P < 0.01). The area under the curve of miR-4286 for diagnosing gastric cancer was0.727, and its specificity and positive predictive value were 90% and 0.872, respectively, which was higher than that of tumor marker CA72-4. Conclusions MiR-4286 is highly expressed in gastric cancer serum, and its expression level is negatively correlated with pathological differentiation. It may be a potential diagnostic marker for gastric cancer.
Objective To investigate the correlation between the expression level of serum miR-4286 and clinicopathological characteristics of gastric cancer, and analyze its efficacy and significance in clinical diagnosis of gastric cancer. Methods Real time fluorescence quantitative PCR was used to detect the expression of miR-4286 in serum samples of healthy control group and gastric cancer group. The correlation between the expression of miR-4286 and the clinicopathological features of gastric cancer was analyzed by statistical methods; Diagnostic efficacy of miR-4286 for gastric cancer was assessed by receiver operating characteristic curve and risk score analysis; Expression of tumor markers CEA, CA19-9, and CA72-4 were detected by electrochemiluminescence immunoassay. Results The expression of miR-4286 in the serum of gastric cancer group was higher than that in healthy control group(Z =-4.644,P < 0.0001). The expression level of miR-4286 in gastric cancer group was not related to tumor clinical stage, lymph node metastasis and distant metastasis(P > 0.05), but it was negatively correlated with the degree of pathological differentiation of tumor cells(Z =-2.661, P < 0.01). Compared with the control group, there was no significant difference in the expression of CEA and CA19-9 in the serum of gastric cancer group(P > 0.05), but the expression of CA72-4 was increased(Z =-3.324, P < 0.01). The area under the curve of miR-4286 for diagnosing gastric cancer was0.727, and its specificity and positive predictive value were 90% and 0.872, respectively, which was higher than that of tumor marker CA72-4. Conclusions MiR-4286 is highly expressed in gastric cancer serum, and its expression level is negatively correlated with pathological differentiation. It may be a potential diagnostic marker for gastric cancer.
引文
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[18]SHEKARI N,BARADARAN B,SHANEHBANDI D,et al.Circulating microRNAs:valuable biomarkers for the diagnosis and prognosis of gastric cancer[J].Curr Med Chem,2018,25(6):698-714.
[2]YIN J,SONG J N,BAI Z G,et al.Gastric cancer mortality trends in China(2006-2013)reveal increasing mortality in young subjects[J].Anticancer Res,2017,37(8):4671-4679.
[3]PRATAP P,RAZA S T,ABBAS S,et al.MicroRNA-associated carcinogenesis in lung carcinoma[J].J Cancer Res Ther,2018,14(2):249-254.
[4]HU W,TAN C,HE Y,et al.Functional miRNAs in breast cancer drug resistance[J].Onco Targets Ther,2018,11:1529-1541.
[5]SAND M,SKRYGAN M,SAND D,et al.Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma,cutaneous malignant melanoma metastases,and benign melanocytic nevi[J].Cell Tissue Res,2013,351(1):85-98.
[6]KOMINA A,PALKINA N,AKSENENKO M,et al.Antiproliferative and pro-apoptotic effects of miR-4286 inhibition in melanoma cells[J].PLoS One,2016,11(12):e0168229.
[7]VANNINI I,FANINI F,FABBRI M.Emerging roles of microRNAs in cancer[J].Curr Opin Genet Dev,2018,48:128-133.
[8]KIAN R,MORADI S,GHORBIAN S.Role of components of microRNA machinery in carcinogenesis[J].Exp Oncol,2018,40(1):2-9.
[9]HOSSEINAHLI N,AGHAPOUR M,DUIJF P H G,et al.Treating cancer withn microRNA replacement therapy:a literature review[J].J Cell Physiol,2018,233(8):5574-5588.
[10]DING B,GAO X,LI H,et al.A novel microRNA signature predicts survival in stomach adenocarcinoma[J].Oncotarget,2017,8(17):28144-28153.
[11]VIRGILIO E,GIARNIERI E,GIOVAGNOLI M R,et al.Gastric juice micrornas as potential biomarkers for screening gastric cancer:a systematic review[J].Anticancer Res,2018,38(2):613-616.
[12]WANG J,LIU Y,SUN W,et al.Plasma exosomes as novel biomarker for the early diagnosis of gastric cancer[J].Cancer Biomark,2018,21(4):805-812.
[13]DRAHOS J,SCHWAMEIS K,ORZOLEK L D,et al.MicroRNAprofiles of Barrett's esophagus and esophageal adenocarcinoma:differences in glandular non-native epithelium[J].Cancer Epidemiol Biomarkers Prev,2016,25(3):429-437.
[14]ZHAI R,WEI Y,SU L,et al.Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma:the influence of Helicobacter pylori infection status[J].Carcinogenesis,2015,36(1):87-93.
[15]LIANG Y,WANG W,FANG C,et al.Clinical significance and diagnostic value of serum CEA,CA19-9 and CA72-4 in patients with gastric cancer[J].Oncotarget,2016,7(31):49565-49573.
[16]YU J,ZHANG S,ZHAO B.Differences and correlation of serum CEA,CA19-9 and CA72-4 in gastric cancer[J].Mol Clin Oncol,2016,4(3):441-449.
[17]GUO J,CHEN S,LI S,et al.A novel classifier based on three preoperative tumor markers predicting the cancer-specific survival of gastric cancer(CEA,CA19-9 and CA72-4)[J].Oncotarget,2017,9(4):4814-4822.
[18]SHEKARI N,BARADARAN B,SHANEHBANDI D,et al.Circulating microRNAs:valuable biomarkers for the diagnosis and prognosis of gastric cancer[J].Curr Med Chem,2018,25(6):698-714.