食管癌组织环状-TTBK2和miR-217表达及临床病理意义
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摘要
目的检测miR-217、环状-TTBK2在食管癌肿瘤组织和癌旁组织中表达情况,探讨miR-217、环状-TTBK2与食管癌患者临床病理特征及预后的关系。方法收集食管癌肿瘤组织及对应癌旁组织各69例,实时荧光定量PCR(qRT-PCR)检测miR-217、环状-TTBK2表达水平,比较并分析miR-217、环状-TTBK2与食管癌患者临床病理特征及预后的关系。结果食管癌肿瘤组织中miR-217表达水平显著低于癌旁组织,差异有统计学意义(P<0.05);环状-TTBK2表达水平显著高于癌旁组织(P<0.05)。食管癌肿瘤组织中miR-217与环状-TTBK2表达呈负相关(r=-0.609,P<0.05)。miR-217、环状-TTBK2表达水平高低与食管癌患者TNM分期、肿瘤分化程度及淋巴结转移有关(P<0.05),与患者年龄、性别、病变部位、病理类型、浸润深度无关(P>0.05)。miR-217低表达患者3年存活率(41.46%)显著低于miR-217高表达者(78.57%,P<0.05),环状-TTBK2低表达者3年存活率(37.21%)明显低于环状-TTBK2高表达者(88.46%,P<0.05)。COX多因素分析显示,miR-217表达、环状-TTBK2表达、TNM分期是影响食管癌患者预后的独立危险因素(HR=2.674,95%CI:1.128～6.339;HR=2.328,95%CI:1.097～4.940;HR=2.907,95%CI:1.573～5.372;P均<0.05)。结论 miR-217在食管癌患者肿瘤组织中低表达,环状-TTBK2高表达,二者表达与食管癌疾病恶性程度及患者预后有关。
Objective To detect the expressions of miR-217 and ring-TTBK2 in tumor tissues and paracancerous tissues of esophageal cancer, and investigate the relationships between miR-217 and ring-TTBK2 with the clinicopathological characteristics and prognosis in patients with esophageal cancer. Methods 69 cases of tumor tissues of esophageal cancer and corresponding paracancerous tissues were collected. Real time fluorescence quantitative PCR(qRT-PCR) was used to detect the expression levels of miR-217 and ring-TTBK2. The relationship between miR-217 and ring-TTBK2 with clinicopathological characteristics and prognosis of esophageal cancer was compared and analyzed. Results The expression level of miR-217 in tumor tissues of esophageal cancer was significantly lower than that in paracancerous tissues, and the difference was statistically significant(P<0.05). The expression level of ring-TTBK2 was significantly higher than that in paracancerous tissues(P<0.05). The expression of miR-217 was negatively correlated with the expression of ring-TTBK2 in tumor tissues of esophageal cancer(r=-0.609, P<0.05). The expression levels of miR-217 and ring-TTBK2 were correlated with TNM stage, differentiation degree and lymph node metastasis of patients with esophageal cancer(P<0.05). They were not related to age, sex, lesion location, pathological type and depth of invasion(P>0.05). The 3 year survival rate of patients with low expression of miR-217(41.46%) was significantly lower than that of patients with high miR-217 expression(78.57%,P<0.05). The 3 year survival rate of patients with low expression of ring-TTBK2(37.21%) was significantly lower than that of patients with ring-TTBK2 with high expression(88.46%,P<0.05). COX multifactor analysis showed that miR-217 expression, ring-TTBK2 expression and TNM staging were independent risk factors for the prognosis of patients with esophageal cancer(HR 2.674, 95% CI 1.128-6.339; HR 2.328, 95% CI 1.097-4.940; HR 2.907, 95% CI 1.573-5.372; P<0.05). Conclusion MiR-217 is low expressed in tumor tissues of esophageal cancer patients, and the ring-TTBK2 is high expressed. Their expression is associated with malignant degree of esophageal cancer and prognosis of patients.
Objective To detect the expressions of miR-217 and ring-TTBK2 in tumor tissues and paracancerous tissues of esophageal cancer, and investigate the relationships between miR-217 and ring-TTBK2 with the clinicopathological characteristics and prognosis in patients with esophageal cancer. Methods 69 cases of tumor tissues of esophageal cancer and corresponding paracancerous tissues were collected. Real time fluorescence quantitative PCR(qRT-PCR) was used to detect the expression levels of miR-217 and ring-TTBK2. The relationship between miR-217 and ring-TTBK2 with clinicopathological characteristics and prognosis of esophageal cancer was compared and analyzed. Results The expression level of miR-217 in tumor tissues of esophageal cancer was significantly lower than that in paracancerous tissues, and the difference was statistically significant(P<0.05). The expression level of ring-TTBK2 was significantly higher than that in paracancerous tissues(P<0.05). The expression of miR-217 was negatively correlated with the expression of ring-TTBK2 in tumor tissues of esophageal cancer(r=-0.609, P<0.05). The expression levels of miR-217 and ring-TTBK2 were correlated with TNM stage, differentiation degree and lymph node metastasis of patients with esophageal cancer(P<0.05). They were not related to age, sex, lesion location, pathological type and depth of invasion(P>0.05). The 3 year survival rate of patients with low expression of miR-217(41.46%) was significantly lower than that of patients with high miR-217 expression(78.57%,P<0.05). The 3 year survival rate of patients with low expression of ring-TTBK2(37.21%) was significantly lower than that of patients with ring-TTBK2 with high expression(88.46%,P<0.05). COX multifactor analysis showed that miR-217 expression, ring-TTBK2 expression and TNM staging were independent risk factors for the prognosis of patients with esophageal cancer(HR 2.674, 95% CI 1.128-6.339; HR 2.328, 95% CI 1.097-4.940; HR 2.907, 95% CI 1.573-5.372; P<0.05). Conclusion MiR-217 is low expressed in tumor tissues of esophageal cancer patients, and the ring-TTBK2 is high expressed. Their expression is associated with malignant degree of esophageal cancer and prognosis of patients.
引文
1 乔友林.食管癌流行病学研究的重要里程碑[J].中国肿瘤临床,2016,43(12):500-501
2 诸葛雪朋,孟庆江,王保收.食管癌组织MTA1蛋白表达与患者临床病理特征及3年生存率的关系[J].重庆医学,2017,46(31):4378-4380
3 Slaby O,Srovnal J,Radova L,et al.Dynamic changes in microRNA expression profiles reflect progression of Barrett′s esophagus to esophageal adenocancer[J].Carcinogenesis,2015,36(5):521-527
4 Li J,Li D,Zhang W.Tumor suppressor role of miR-217 in human epithelial ovarian cancer by targeting IGF1R[J].Oncol Rep,2016,35(3):1671-1679
5 Haque S,Harries LW.Circular RNAs (circRNAs) in health and disease[J].Genes,2017,8(12):353-362
6 Jian Z,Liu X,Xue Y,et al.TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway[J].J Hematol Oncol,2017,10(1):52-70
7 Yamasaki M,Miyata H,Miyazaki Y,et al.Evaluation of the nodal status in the 7th edition of the UICC-TNM classification for esophageal squamous cell cancer:proposed modifications for improved survival stratification :impact of lymph node metastases on overall survival after esophagectomy[J].Ann Surg Oncol,2014,21(9):2850-2856
8 傅剑华,谭子辉.食管癌外科治疗的现状与未来展望[J].中国肿瘤临床,2016,43(12):507-510
9 Alsop BR,Sharma P.Esophageal cancer[J].Gastroenterol Clin N,2016,45(3):399-412
10 Zhou W,Song F,Wu Q,et al.miR-217 inhibits triple-negative breast cancer cell growth,migration,and invasion through targeting KLF5[J].PLoS One,2017,12(4):e0176395-11
11 Ansari MH,Irani S,Edalat H,et al.Deregulation of miR-93,and miR-143,in human esophageal cancer[J].Tumor Biol,2016,37(3):3097-3103
12 Wang Z,Qiao Q,Chen M,et al.miR-625 down-regulation promotes proliferation and invasion in esophageal cancer by targeting Sox2[J].FEBS Lett,2014,588(6):915-921
13 Winther M,Alsner J,Tramm T,et al.Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer[J].Acta Oncol,2015,54(9):1582-1591
14 Su J,Wang Q,Liu Y,et al.miR-217 inhibits invasion of hepatocellular cancer cells through direct suppression of E2F3[J].Mol Cell Biochem,2014,392(1-2):289-296
15 Lin Y,Cheng K,Wang T,et al.miR-217 inhibits proliferation,migration,and invasion via targeting AKT3 in thyroid cancer[J].Biomed Pharmacother,2017,36(5):1718-1724
16 Zhang N,Lu C,Chen L.miR-217 regulates tumor growth and apoptosis by targeting the MAPK signaling pathway in colorectal cancer[J].Oncol Lett,2016,12(6):4589-4597
17 Li P,Chen S,Chen H,et al.Using circular RNA as a novel type of biomarker in the screening of gastric cancer[J].Clin Chim Acta,2015,60(4):132-136
18 Hsiao KY,Lin YC,Gupta SK,et al.Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis[J].Cancer Res,2017,77(9):2339-2350
19 Liao JC,Yang TT,Weng RR,et al.TTBK2:a Tau protein kinase beyond Tau phosphorylation[J].Biomed Res Int,2015,75(4):1-10
20 Bender C,Ullrich A.PRKX,TTBK2 and RSK4 expression causes sunitinib resistance in kidney cancer-and melanoma-cell lines[J].Int J Cancer,2012,131(2):E45-55
21 Zheng J,Liu X,Xue Y,et al.TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway[J].J Hematol Oncol,2017,10(1):52-61
2 诸葛雪朋,孟庆江,王保收.食管癌组织MTA1蛋白表达与患者临床病理特征及3年生存率的关系[J].重庆医学,2017,46(31):4378-4380
3 Slaby O,Srovnal J,Radova L,et al.Dynamic changes in microRNA expression profiles reflect progression of Barrett′s esophagus to esophageal adenocancer[J].Carcinogenesis,2015,36(5):521-527
4 Li J,Li D,Zhang W.Tumor suppressor role of miR-217 in human epithelial ovarian cancer by targeting IGF1R[J].Oncol Rep,2016,35(3):1671-1679
5 Haque S,Harries LW.Circular RNAs (circRNAs) in health and disease[J].Genes,2017,8(12):353-362
6 Jian Z,Liu X,Xue Y,et al.TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway[J].J Hematol Oncol,2017,10(1):52-70
7 Yamasaki M,Miyata H,Miyazaki Y,et al.Evaluation of the nodal status in the 7th edition of the UICC-TNM classification for esophageal squamous cell cancer:proposed modifications for improved survival stratification :impact of lymph node metastases on overall survival after esophagectomy[J].Ann Surg Oncol,2014,21(9):2850-2856
8 傅剑华,谭子辉.食管癌外科治疗的现状与未来展望[J].中国肿瘤临床,2016,43(12):507-510
9 Alsop BR,Sharma P.Esophageal cancer[J].Gastroenterol Clin N,2016,45(3):399-412
10 Zhou W,Song F,Wu Q,et al.miR-217 inhibits triple-negative breast cancer cell growth,migration,and invasion through targeting KLF5[J].PLoS One,2017,12(4):e0176395-11
11 Ansari MH,Irani S,Edalat H,et al.Deregulation of miR-93,and miR-143,in human esophageal cancer[J].Tumor Biol,2016,37(3):3097-3103
12 Wang Z,Qiao Q,Chen M,et al.miR-625 down-regulation promotes proliferation and invasion in esophageal cancer by targeting Sox2[J].FEBS Lett,2014,588(6):915-921
13 Winther M,Alsner J,Tramm T,et al.Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer[J].Acta Oncol,2015,54(9):1582-1591
14 Su J,Wang Q,Liu Y,et al.miR-217 inhibits invasion of hepatocellular cancer cells through direct suppression of E2F3[J].Mol Cell Biochem,2014,392(1-2):289-296
15 Lin Y,Cheng K,Wang T,et al.miR-217 inhibits proliferation,migration,and invasion via targeting AKT3 in thyroid cancer[J].Biomed Pharmacother,2017,36(5):1718-1724
16 Zhang N,Lu C,Chen L.miR-217 regulates tumor growth and apoptosis by targeting the MAPK signaling pathway in colorectal cancer[J].Oncol Lett,2016,12(6):4589-4597
17 Li P,Chen S,Chen H,et al.Using circular RNA as a novel type of biomarker in the screening of gastric cancer[J].Clin Chim Acta,2015,60(4):132-136
18 Hsiao KY,Lin YC,Gupta SK,et al.Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis[J].Cancer Res,2017,77(9):2339-2350
19 Liao JC,Yang TT,Weng RR,et al.TTBK2:a Tau protein kinase beyond Tau phosphorylation[J].Biomed Res Int,2015,75(4):1-10
20 Bender C,Ullrich A.PRKX,TTBK2 and RSK4 expression causes sunitinib resistance in kidney cancer-and melanoma-cell lines[J].Int J Cancer,2012,131(2):E45-55
21 Zheng J,Liu X,Xue Y,et al.TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway[J].J Hematol Oncol,2017,10(1):52-61