miR-200a-3p和G3BP2表达与胃癌临床病理特征的关系
|
摘要
目的探究微小RNA-200a-3p(miR-200a-3p)和GTP酶激活蛋白SH3功能结合蛋白2(G3BP2)表达水平及其与胃癌临床病理特征的关系。方法选取本院收治的102例胃癌患者为研究对象,取本组所有胃癌患者的胃癌组织标本及癌旁正常组织标本。采用实时荧光定量PCR技术检测患者胃癌组织、癌旁正常组织中miR-200a-3p和G3BP2 mRNA相对表达量,收集分析胃癌患者临床病理特征,Kaplan-Meier对胃癌患者生存情况进行分析,COX回归分析影响胃癌发生的危险因素。结果胃癌组织miR-200a-3p表达水平显著低于癌旁正常组织(P <0. 05),G3BP2表达水平显著高于癌旁正常组织(P <0. 05);Pearson相关性分析表明miR-200a-3p和G3BP2 mRNA表达水平呈负相关(r=-0. 417,P <0. 05)。免疫组化结果表明胃癌组织G3BP2蛋白表达阳性率显著高于癌旁正常组织(P <0. 05)。miR-200a-3p和G3BP2表达水平与胃癌分化程度和TNM分期有关(P <0. 05)。Kaplan-Meier法分析结果显示miR-200a-3p低表达组3年生存率均显著低于高表达组(P <0. 05),G3BP2高表达组3年生存率均显著高于低表达组(P <0. 05)。COX回归分析结果显示miR-200a-3p、G3BP2表达为影响胃癌发生的独立危险因素。结论胃癌组织miR-200a-3p表达下调,G3BP2表达上调,二者表达与胃癌发生及发展有关,可作为临床评估患者预后的参考指标。
Objective To investigate the expression of microRNA-200 a-3 p( miR-200 a-3 p) and GTP enzyme activator protein SH3 binding protein 2( G3 BP2) and their relationships with clinicopathological features of gastric cancer. Methods One hundred and two patients with gastric cancer in our hospital were selected as the research subjects. The specimens of gastric cancer tissues and adjacent normal tissues were collected to detect the relative expression of miR-200 a-3 p and G3 BP2 mRNA by real-time fluorescence quantitative PCR. The clinicopathological characteristics of patients with gastric cancer were collected and analyzed. The survival rate of gastric cancer patients was analyzed by Kaplan-Meier,and COX regression analysis was used to analyze the risk factors influencing the occurrence of gastric cancer. Results The expression of miR-200 a-3 p in gastric cancer tissues was significantly lower than that in adjacent normal tissues( P < 0. 05),while the expression of G3 BP2 was significantly higher than that in adjacent normal tissues( P < 0. 05).Pearson correlation analysis showed that miR-200 a-3 p and G3 BP2 mRNA expression levels were negatively correlated( P < 0. 05). The results of immunohistochemistry showed that the positive rate of G3 BP2 protein expression in gastric cancer tissues was significantly higher than that in adjacent normal tissues( P < 0. 05). The expression levels of miR-200 a-3 p and G3 BP2 were correlated with the degree of differentiation and TNM staging of gastric cancer( P < 0. 05). Kaplan-Meier analysis showed that the 3-year survival rate in low microRNA-200 a-3 p expression group was significantly lower than that in high-expression group( P < 0. 05),and the 3-year survival rate in high G3 BP2 expression group was significantly higher than that in low-expression group( P < 0. 05). COX regression analysis showed that miR-200 a-3 p and G3 BP2 were independent risk factors for gastric cancer. Conclusion The expression of miR-200 a-3 p is downregulated and G3 BP2 is up-regulated in gastric cancer tissues,and their expression is related to the occurrence and development of gastric cancer. The miR-200 a-3 p and G3 BP2 can be used as reference indexes for clinical prognosis.
Objective To investigate the expression of microRNA-200 a-3 p( miR-200 a-3 p) and GTP enzyme activator protein SH3 binding protein 2( G3 BP2) and their relationships with clinicopathological features of gastric cancer. Methods One hundred and two patients with gastric cancer in our hospital were selected as the research subjects. The specimens of gastric cancer tissues and adjacent normal tissues were collected to detect the relative expression of miR-200 a-3 p and G3 BP2 mRNA by real-time fluorescence quantitative PCR. The clinicopathological characteristics of patients with gastric cancer were collected and analyzed. The survival rate of gastric cancer patients was analyzed by Kaplan-Meier,and COX regression analysis was used to analyze the risk factors influencing the occurrence of gastric cancer. Results The expression of miR-200 a-3 p in gastric cancer tissues was significantly lower than that in adjacent normal tissues( P < 0. 05),while the expression of G3 BP2 was significantly higher than that in adjacent normal tissues( P < 0. 05).Pearson correlation analysis showed that miR-200 a-3 p and G3 BP2 mRNA expression levels were negatively correlated( P < 0. 05). The results of immunohistochemistry showed that the positive rate of G3 BP2 protein expression in gastric cancer tissues was significantly higher than that in adjacent normal tissues( P < 0. 05). The expression levels of miR-200 a-3 p and G3 BP2 were correlated with the degree of differentiation and TNM staging of gastric cancer( P < 0. 05). Kaplan-Meier analysis showed that the 3-year survival rate in low microRNA-200 a-3 p expression group was significantly lower than that in high-expression group( P < 0. 05),and the 3-year survival rate in high G3 BP2 expression group was significantly higher than that in low-expression group( P < 0. 05). COX regression analysis showed that miR-200 a-3 p and G3 BP2 were independent risk factors for gastric cancer. Conclusion The expression of miR-200 a-3 p is downregulated and G3 BP2 is up-regulated in gastric cancer tissues,and their expression is related to the occurrence and development of gastric cancer. The miR-200 a-3 p and G3 BP2 can be used as reference indexes for clinical prognosis.
引文
[1]左婷婷,郑荣寿,曾红梅,等.中国胃癌流行病学现状[J].中国肿瘤临床,2017,44(1):52-58.
[2]陈志凯,傅松维,鲍舟君,等.胃癌患者血清miR-200b和miR-200c水平变化及临床意义[J].中国生化药物杂志,2016,36(5):201-203.
[3] Chapelle N,Bouvier AM,Manfredi S,et al. Early gastric cancer:trends in incidence,management,and survival in a well-defined french population[J]. Ann Surg Oncol,2016,23(11):1-7.
[4] Inoguchi S,Seki N,Chiyomaru T,et al. Tumour-suppressive microRNA-24-1 inhibits cancer cell proliferation through targeting FOXM1 in bladder cancer[J]. FEBS Lett,2016,588(17):3170-3179.
[5] Luebeck EG,Curtius K,Jeon J,et al. Impact of tumor progression on cancer incidence curves[J]. Cancer Res,2013,73(3):1086-1096.
[6]刘丹丹,刘洁,赵亚刚.消化道恶性肿瘤与顺铂耐药相关性的研究进展[J].广东医学,2018,39(6):803-806.
[7]侯冰冰,张力图.结直肠癌肝转移相关miRNA的研究进展[J].山东医药,2017,57(40):108-110.
[8]马大昌,陈诚,吴多明,等. miR-199a-3p在乳腺癌中的表达及其作用[J].中国癌症杂志,2016,26(6):481-486.
[9]梁治坤,程几天,胡走肖,等. miR-150-5p抑制肝癌细胞的迁移和侵袭及其机制[J].中国普通外科杂志,2016,25(8):1175-1179.
[10] Wang Z,Ma X,Cai Q,et al. MiR-199a-3p promotes gastric cancer progression by targeting ZHX1[J]. FEBS Lett,2016,588(23):4504-4512.
[11] Zhang Y,Wen X,Hu XL,et al. Downregulation of miR-145-5p correlates with poor prognosis in gastric cancer[J]. Eur Rev Med Pharmacol Sci,2016,20(14):3026-3030.
[12] Li Y,Nie Y,Tu S,et al. Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells[J]. Oncol Rep,2016,36(4):2108-2116.
[13]唐峰波,杨铭. MiR-200家族与消化道肿瘤的相关研究[J].中华临床医师杂志:电子版,2016,10(1):110-115.
[14] Hong HQ,Lu J,Fang XL,et al. G3BP2 is involved in isoproterenol-induced cardiac hypertrophy through activating the NF-κB signaling pathway[J]. Acta Pharmacol Sin,2017,39(2):184-194.
[15] Dou N,Chen J,Yu S,et al. G3BP1 contributes to tumor metastasis via upregulation of Slug expression in hepatocellular carcinoma[J]. Am J Cancer Res,2016,6(11):2641-2650.
[16] Gupta N,Badeaux M,Liu Y,et al. Stress granule-associated protein G3BP2 regulates breast tumor initiation[J]. Proc Natl Acad Sci U S A,2017,114(5):1033-1038.
[17] Takayama K,Suzuki T,Tanaka T,et al. TRIM25 enhances cell growth and cell survival by modulating p53 signals via interaction with G3BP2 in prostate cancer[J]. Oncogene,2018,37(16):2165-2180.
[18] Zhao B,Li H,Liu J,et al. MicroRNA-23b targets Ras GTPaseactivating protein SH3 domain-binding protein 2 to alleviate fibrosis and albuminuria in diabetic nephropathy[J]. J Am Soc Nephrol,2016,27(9):2597-2608.
[2]陈志凯,傅松维,鲍舟君,等.胃癌患者血清miR-200b和miR-200c水平变化及临床意义[J].中国生化药物杂志,2016,36(5):201-203.
[3] Chapelle N,Bouvier AM,Manfredi S,et al. Early gastric cancer:trends in incidence,management,and survival in a well-defined french population[J]. Ann Surg Oncol,2016,23(11):1-7.
[4] Inoguchi S,Seki N,Chiyomaru T,et al. Tumour-suppressive microRNA-24-1 inhibits cancer cell proliferation through targeting FOXM1 in bladder cancer[J]. FEBS Lett,2016,588(17):3170-3179.
[5] Luebeck EG,Curtius K,Jeon J,et al. Impact of tumor progression on cancer incidence curves[J]. Cancer Res,2013,73(3):1086-1096.
[6]刘丹丹,刘洁,赵亚刚.消化道恶性肿瘤与顺铂耐药相关性的研究进展[J].广东医学,2018,39(6):803-806.
[7]侯冰冰,张力图.结直肠癌肝转移相关miRNA的研究进展[J].山东医药,2017,57(40):108-110.
[8]马大昌,陈诚,吴多明,等. miR-199a-3p在乳腺癌中的表达及其作用[J].中国癌症杂志,2016,26(6):481-486.
[9]梁治坤,程几天,胡走肖,等. miR-150-5p抑制肝癌细胞的迁移和侵袭及其机制[J].中国普通外科杂志,2016,25(8):1175-1179.
[10] Wang Z,Ma X,Cai Q,et al. MiR-199a-3p promotes gastric cancer progression by targeting ZHX1[J]. FEBS Lett,2016,588(23):4504-4512.
[11] Zhang Y,Wen X,Hu XL,et al. Downregulation of miR-145-5p correlates with poor prognosis in gastric cancer[J]. Eur Rev Med Pharmacol Sci,2016,20(14):3026-3030.
[12] Li Y,Nie Y,Tu S,et al. Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells[J]. Oncol Rep,2016,36(4):2108-2116.
[13]唐峰波,杨铭. MiR-200家族与消化道肿瘤的相关研究[J].中华临床医师杂志:电子版,2016,10(1):110-115.
[14] Hong HQ,Lu J,Fang XL,et al. G3BP2 is involved in isoproterenol-induced cardiac hypertrophy through activating the NF-κB signaling pathway[J]. Acta Pharmacol Sin,2017,39(2):184-194.
[15] Dou N,Chen J,Yu S,et al. G3BP1 contributes to tumor metastasis via upregulation of Slug expression in hepatocellular carcinoma[J]. Am J Cancer Res,2016,6(11):2641-2650.
[16] Gupta N,Badeaux M,Liu Y,et al. Stress granule-associated protein G3BP2 regulates breast tumor initiation[J]. Proc Natl Acad Sci U S A,2017,114(5):1033-1038.
[17] Takayama K,Suzuki T,Tanaka T,et al. TRIM25 enhances cell growth and cell survival by modulating p53 signals via interaction with G3BP2 in prostate cancer[J]. Oncogene,2018,37(16):2165-2180.
[18] Zhao B,Li H,Liu J,et al. MicroRNA-23b targets Ras GTPaseactivating protein SH3 domain-binding protein 2 to alleviate fibrosis and albuminuria in diabetic nephropathy[J]. J Am Soc Nephrol,2016,27(9):2597-2608.