血清长链非编码RNA LNC00993联合MMP-2和CEA在食管癌诊断和预后中的研究
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摘要
目的:探究血清长链非编码RNA(long non-coding RNA,lncRNA)LNC00993、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)与癌胚抗原(carcinoembryonic antigen,CEA)在食管癌诊断和预后中的研究。方法:120例食管癌患者设为病例组,同期体检的健康人群120例设为对照组。采用实时荧光定量PCR(real-time PCR,RT-PCR)法检测血清LNC00993;采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)和化学发光法分别检测MMP-2与CEA水平。结果:病例组的血清LNC00993、MMP-2与CEA水平均显著高于对照组,且差异具有统计学意义(P<0.05)。食管癌患者血清LNC00993、MMP-2与CEA水平与肿瘤TNM分期、组织学类型、肿瘤分化程度等显著相关(P<0.05),且在中晚期食管癌、食管腺鳞癌及低分化食管癌患者中的增高最为显著。LNC00993联合MMP-2与CEA在区分食管癌与对照的曲线下面积(area under the curve,AUC)为0.937(95%CI:0.842～0.981,P<0.001),灵敏度为92.7%,特异度为81.8%。III-IV期患者中,相比低LNC00993组,高LNC00993组患者的生存时间显著缩短(χ~2=4.138,P=0.047);相比低MMP-2组,高MMP-2组患者的生存时间显著缩短(χ~2=11.369,P=0.002);而高CEA组与低CEA组间的生存时间差异无统计学意义(χ~2=0.258,P=0.715)。I-II期患者中,相比低LNC00993组,高LNC00993组患者的生存时间显著缩短(χ~2=7.265,P=0.020);相比低MMP-2组,高MMP-2组患者的生存时间显著缩短(χ~2=9.694,P=0.002);而高CEA组与低CEA组间的生存时间差异无统计学意义(χ~2=0.137,P=0.924)。结论:血清LNC00993、MMP-2与CEA对食管癌具有诊断价值,且与食管癌的TNM分期、组织学类型、分化程度显著相关。此外,血清LNC00993和MMP-2在评估食管癌患者预后具有重要临床意义。
Objective:To investigate the role of serum long non-coding RNA(lncRNA) LNC00993,matrix metalloproteinase-2(MMP-2) and carcinoembryonic antigen(CEA) in the diagnosis and prognosis of esophageal cancer.Methods:120 patients with esophageal cancer were selected as the case group and 120 healthy people as the control group.Real-time fluorescence quantitative PCR(RT-PCR) was used to detect serum LNC00993,and enzyme-linked immunosorbent assay(ELISA) and chemiluminescence were used to detect the levels of MMP-2 and CEA,respectively.Results:The serum levels of LNC00993,MMP-2 and CEA in the case group were significantly higher than those in the control group(P<0.05).The serum levels of LNC00993,MMP-2 and CEA were significantly correlated with tumor TNM stage,histological type and tumor differentiation degree(P<0.05).The serum levels of LNC00993,MMP-2 and CEA were significantly higher in patients with advanced esophageal cancer,adenosquamous carcinoma and poorly differentiated esophageal cancer.When combined with LNC00993,MMP-2 and CEA,the area under the curve(AUC) to distinguish between esophageal cancer and healthy subjects was 0.937(95% CI:0.842～0.981,P<0.001),the sensitivity was 92.7%,and the specificity was 81.8%.In patients with stage III-IV,the survival time was significantly shorter in the high LNC00993 group compared with the low LNC00993 group(χ~2=4.138,P=0.047),compared with the low MMP-2 group,the survival time of the high MMP-2 group was significantly shorted(χ~2=11.369,P=0.002),and there was no significant difference in survival time between high CEA group and low CEA group(χ~2=0.258,P=0.715).In patients with stage I-II,the survival time was significantly shorter in the high LNC00993 group compared with the low LNC00993 group(χ~2=7.265,P=0.020),compared with the low MMP-2 group,the survival time of the high MMP-2 group was significantly shorted(χ~2=9.694,P=0.002),while there was no significant difference in survival time between the high CEA group and the low CEA group(χ~2=0.137,P=0.924).Conclusion:Serum LNC00993,MMP-2 and CEA have diagnostic value for esophageal cancer,and are significantly correlated with TNM stage,histological type and differentiation of esophageal cancer.In addition,serum LNC00993 and MMP-2 have important clinical significance in evaluating the prognosis of patients with esophageal cancer.
Objective:To investigate the role of serum long non-coding RNA(lncRNA) LNC00993,matrix metalloproteinase-2(MMP-2) and carcinoembryonic antigen(CEA) in the diagnosis and prognosis of esophageal cancer.Methods:120 patients with esophageal cancer were selected as the case group and 120 healthy people as the control group.Real-time fluorescence quantitative PCR(RT-PCR) was used to detect serum LNC00993,and enzyme-linked immunosorbent assay(ELISA) and chemiluminescence were used to detect the levels of MMP-2 and CEA,respectively.Results:The serum levels of LNC00993,MMP-2 and CEA in the case group were significantly higher than those in the control group(P<0.05).The serum levels of LNC00993,MMP-2 and CEA were significantly correlated with tumor TNM stage,histological type and tumor differentiation degree(P<0.05).The serum levels of LNC00993,MMP-2 and CEA were significantly higher in patients with advanced esophageal cancer,adenosquamous carcinoma and poorly differentiated esophageal cancer.When combined with LNC00993,MMP-2 and CEA,the area under the curve(AUC) to distinguish between esophageal cancer and healthy subjects was 0.937(95% CI:0.842～0.981,P<0.001),the sensitivity was 92.7%,and the specificity was 81.8%.In patients with stage III-IV,the survival time was significantly shorter in the high LNC00993 group compared with the low LNC00993 group(χ~2=4.138,P=0.047),compared with the low MMP-2 group,the survival time of the high MMP-2 group was significantly shorted(χ~2=11.369,P=0.002),and there was no significant difference in survival time between high CEA group and low CEA group(χ~2=0.258,P=0.715).In patients with stage I-II,the survival time was significantly shorter in the high LNC00993 group compared with the low LNC00993 group(χ~2=7.265,P=0.020),compared with the low MMP-2 group,the survival time of the high MMP-2 group was significantly shorted(χ~2=9.694,P=0.002),while there was no significant difference in survival time between the high CEA group and the low CEA group(χ~2=0.137,P=0.924).Conclusion:Serum LNC00993,MMP-2 and CEA have diagnostic value for esophageal cancer,and are significantly correlated with TNM stage,histological type and differentiation of esophageal cancer.In addition,serum LNC00993 and MMP-2 have important clinical significance in evaluating the prognosis of patients with esophageal cancer.
引文
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[2] 陈鹭,黄晓俊,孙洋.早期食管癌的内镜诊断进展[J].世界华人消化杂志,2016,24(1):51-58.
[3] 彭卓,牛泽群,万林,等.长链非编码RNA MALAT1与非小细胞肺癌患者肿瘤复发和预后的相关性研究[J].实用癌症杂志,2017,32(7):1056-1058,1072.
[4] Chan OTM,Furuya H,Pagano I,et al.Association of MMP-2,RB and PAI-1 with decreased recurrence-free survival and overall survival in bladder cancer patients[J].Oncotarget,2017,8(59):99707-99721.
[5] Jiang M,Xiao Y,Liu D,et al.Overexpression of long noncoding RNA LINC01296 indicates an unfavorable prognosis and promotes tumorigenesis in breast cancer[J].Gene,2018,675:217-224.
[6] Wu Q,Guo L,Jiang F,et al.Analysis of the miRNA-mRNA-lncRNA networks in ER+ and ER- breast cancer cell lines[J].J Cell Mol Med.2015,19(12):2874-2887.
[7] Chen R,Xia W,Wang X,et al.Upregulated long non-coding RNA SBF2-AS1 promotes proliferation in esophageal squamous cell carcinoma[J].Oncol Lett,2018,15(4):5071-5080.
[8] Huang ZL,Chen RP,Zhou XT,et al.Long non-coding RNA MEG3 induces cell apoptosis in esophageal cancer through endoplasmic reticulum stress[J].Oncol Rep,2017,37(5):3093-3099.
[9] Chen C,Li Z,Yang Y,et al.Microarray expression profiling of dysregulated long non-coding RNAs in triple-negative breast cancer[J].Cancer Biol Ther.2015,16(6):856-865.
[10] Li Y,Sun B,Zhao X,et al.MMP-2 and MMP-13 affect vasculogenic mimicry formation in large cell lung cancer[J].J Cell Mol Med,2017,21(12):3741-3751.
[11] Nosratzehi T,Alijani E,Moodi M.Salivary MMP-1,MMP-2,MMP-3 and MMP-13 Levels in Patients with Oral Lichen Planus and Squamous Cell Carcinoma[J].Asian Pac J Cancer Prev,2017,18(7):1947-1951.
[12] Pei L,He X,Li S,et al.KRAB zinc-finger protein 382 regulates epithelial-mesenchymal transition and functions as a tumor suppressor,but is silenced by CpG methylation in gastric cancer[J].Int J Oncol,2018,53(3):961-972.
[13] Chien YC,Liu LC,Ye HY,et al.EZH2 promotes migration and invasion of triple-negative breast cancer cells via regulating TIMP2-MMP-2/-9 pathway[J].Am J Cancer Res,2018,8(3):422-434.