前列腺癌组织中miRNA-34c、c-Met mRNA的表达观察
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摘要
目的观察前列腺癌组织中微小RNA-34c(miR-34c)、肝细胞生长因子受体(c-Met) mRNA的表达变化,并探讨其临床意义。方法 63例前列腺癌患者,均行肿瘤切除术,术中保留癌组织; 45例前列腺增生患者,留取前列腺增生组织。采用实时荧光定量PCR法检测前列腺癌组织、前列腺增生组织中miR-34c、c-Met mRNA,分析前列腺癌组织miR-34c、c-Met mRNA表达的相关性,分析miR-34c、c-Met mRNA表达与前列腺癌临床病理参数及预后的关系。结果前列腺癌组织、前列腺增生组织中miR-34c相对表达量分别为0. 521±0. 426、1. 247±0. 681,c-Met mRNA的相对表达量分别为2. 527±0. 348、1. 056±0. 217,两者比较,P均<0. 05。前列腺癌组织中miR-34c、c-Met mRNA表达呈负相关(r=-0. 630,P <0. 05)。miR-34c表达与前列腺癌患者Gleason评分和TNM分期有关(P均<0. 05),c-Met mRNA表达与前列腺癌患者Gleason评分、TNM分期及有无远处转移有关(P均<0. 05)。前列腺癌患者中miR-34c高表达者3、5年总体生存率(OS)分别为84. 85%(28/33)、60. 61%(22/33),miR-34c低表达者分别为70. 00%(21/30)、40. 00%(13/30),两者比较,P均<0. 05;前列腺癌患者中c-Met mRNA高表达者3、5年OS分别为68. 51%(24/35)、37. 14%(13/35),c-Met mRNA低表达者分别为89. 29%(25/28)、78. 57%(22/28),两者比较,P均<0. 05。结论前列腺癌组织miR-34c低表达、c-Met mRNA高表达,两者可能参与前列腺癌的发生发展。
Objective To investigate the expression of miR-34 c and c-Met in prostate cancer tissues,and to explore its clinical significance. Methods Sixty-three patients with prostate cancer underwent tumor resection,and the cancer tissues were preserved during operation; the prostate hyperplasia tissues from 45 patients with benign prostatic hyperplasia were collected. The real-time quantitative PCR was used to detect miR-34 c and c-Met mRNA in prostate cancer tissues and benign prostatic hyperplasia tissues. The correlation of miR-34 c and c-Met mRNA expression in prostate cancer tissues was analyzed,and the relationships of miR-34 c and c-Met mRNA expression with the clinicopathological parameters and prognosis in patients with prostate cancer were also analyzed. Results The relative expression levels of microRNAs-34 c in the prostate cancer and benign prostatic hyperplasia were 0. 521 ± 0. 426 and 1. 247 ± 0. 681,with statistically significant difference( P < 0. 05). The relative expression of c-Met mRNA in the prostate cancer and benign prostatic hyperplasia tissues were 2. 527 ± 0. 348 and 1. 056 ± 0. 217,with statistically significant difference( P < 0. 05). There was a negative correlation between miR-34 c and c-Met mRNA expression in prostate cancer( r =-0. 630,P < 0. 05). The expression of microRNA-34 c was correlated with Gleason score and TNM stage( both P < 0. 05). The expression of c-MetmRNA was correlated with Gleason score,TNM stage and distant metastasis( all P < 0. 05). The overall 3-year survival rate( OS) and 5-a-OS were 84. 85%( 28/33) and 60. 61%( 22/33) in patients with prostate cancer,70. 00%( 21/30) and 40. 00%( 13/30) in patients with low expression of Mi-34 c,respectively. Kaplan-Meier analysis( log-rank test) showed that 3-a OS and 5-a-OS were significantly higher in patients with high expression of Mi-34 c. The expression of 3A OS and 5A OS were 68. 51%( 24/35) and 37. 14%( 13/35) in patients with prostate cancer,89. 29%( 25/28) and 78. 57%( 22/28)in patients with low expression of c-MetmRNA,and 89. 29%( 25/28) and 78. 57%( 22/28) in patients with low expression of c-MetmRNA,with statistically significant difference( all P < 0. 05). Conclusion In the prostate cancer tissues,miR-34c is low expressed and c-Met mRNA is highly expressed,both of which may be involved in the occurrence and development of prostate cancer.
Objective To investigate the expression of miR-34 c and c-Met in prostate cancer tissues,and to explore its clinical significance. Methods Sixty-three patients with prostate cancer underwent tumor resection,and the cancer tissues were preserved during operation; the prostate hyperplasia tissues from 45 patients with benign prostatic hyperplasia were collected. The real-time quantitative PCR was used to detect miR-34 c and c-Met mRNA in prostate cancer tissues and benign prostatic hyperplasia tissues. The correlation of miR-34 c and c-Met mRNA expression in prostate cancer tissues was analyzed,and the relationships of miR-34 c and c-Met mRNA expression with the clinicopathological parameters and prognosis in patients with prostate cancer were also analyzed. Results The relative expression levels of microRNAs-34 c in the prostate cancer and benign prostatic hyperplasia were 0. 521 ± 0. 426 and 1. 247 ± 0. 681,with statistically significant difference( P < 0. 05). The relative expression of c-Met mRNA in the prostate cancer and benign prostatic hyperplasia tissues were 2. 527 ± 0. 348 and 1. 056 ± 0. 217,with statistically significant difference( P < 0. 05). There was a negative correlation between miR-34 c and c-Met mRNA expression in prostate cancer( r =-0. 630,P < 0. 05). The expression of microRNA-34 c was correlated with Gleason score and TNM stage( both P < 0. 05). The expression of c-MetmRNA was correlated with Gleason score,TNM stage and distant metastasis( all P < 0. 05). The overall 3-year survival rate( OS) and 5-a-OS were 84. 85%( 28/33) and 60. 61%( 22/33) in patients with prostate cancer,70. 00%( 21/30) and 40. 00%( 13/30) in patients with low expression of Mi-34 c,respectively. Kaplan-Meier analysis( log-rank test) showed that 3-a OS and 5-a-OS were significantly higher in patients with high expression of Mi-34 c. The expression of 3A OS and 5A OS were 68. 51%( 24/35) and 37. 14%( 13/35) in patients with prostate cancer,89. 29%( 25/28) and 78. 57%( 22/28)in patients with low expression of c-MetmRNA,and 89. 29%( 25/28) and 78. 57%( 22/28) in patients with low expression of c-MetmRNA,with statistically significant difference( all P < 0. 05). Conclusion In the prostate cancer tissues,miR-34c is low expressed and c-Met mRNA is highly expressed,both of which may be involved in the occurrence and development of prostate cancer.
引文
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[13]Hagman Z,Haflidadottir BS,Ansari M,et al.The tumour suppressor miR-34c targets MET in prostate cancer cells[J].Br JCancer,2013,109(5):1271-1278.
[14]Li H,Rokavec M,Jiang L,et al.Antagonistic effects of p53 and HIF1A on microRNA-34a regulation of PPP1R11 and STAT3 and hypoxia-induced epithelial to mesenchymal transition in colorectal cancer cells[J].Gastroenterology,2017,153(2):505-520.
[15]Jacobsen F,Ashtiani SN,Tennstedt P,et al.High c-MET expression is frequent but not associated with early PSA recurrence in prostate cancer[J].Exp Ther Med,2013,5(1):102-106.
[16]Kitajima Y,Ide T,Ohtsuka T,et al.Induction of hepatocyte growth factor activator gene expression under hypoxia activates the hepatocyte growth factor/c-Met system via hypoxia inducible factor-1 in pancreatic cancer[J].Cancer Sci,2008,99(7):1341-1347.
[17]Han Y,Luo Y,Zhao J,et al.Overexpression of c-Met increases the tumor invasion of human prostate LNCaP cancer cells in vitro and in vivo[J].Oncol Iett,2014,8(4):1618-1624.
[18]黄远见,肖娟,张志伟,等.miR-34a抑制人鼻咽癌细胞生长与侵袭[J].中南医学科学杂志,2014,42(3):251-254.
[19]Hagman Z,Haflidadottir BS,Ansari M,et al.The tumour suppressor miR-34c targets MET in prostate cancer cells[J].Br JCancer,2013,109(5):1271-1278.
[20]Moumen A,Patane S,Porras A,et al.Met acts on Mdm2 via m TOR to signal cell survival during development[J].Development,2007,134(7):1443-1451.
[2]Chen JG,Chen HZ,Zhu J,et al.Cancer survival in patients from a hospital-based cancer registry,China[J].J Cancer,2018,9(5):851-860.
[3]Crawford ED,Higano CS,Shore ND,et al.Treating patients with metastatic castration resistant prostate cancer:a comprehensive review of available therapies[J].J Urol,2015,194(6):1537-1547.
[4]Fabris L,Ceder Y,Chinnaiyan AM,et al.The potential of MicroRNAs as prostate cancer biomarkers[J].Eur Urol,2016,70(2):312-322.
[5]Wang L,Yu J,Xu J,et al.The analysis of microRNA-34 family expression in human cancer studies comparing cancer tissues with corresponding pericarcinous tissues[J].Gene,2015,554(1):1-8.
[6]邵新宏,张才全.miR-34a慢病毒表达质粒的构建及其对人结肠癌SW480细胞增殖的作用[J].中国生物制品学杂志,2013,26(6):807-812.
[7]王友娟,吴秋华,杨娟,等.miR-34c对人喉癌细胞株Hep-2细胞的影响[J].江苏医药,2014,40(4):392-394.
[8]Varkaris A,Corn PG,Gaur S,et al.The role of HGF/c-Met signaling in prostate cancer progression and c-Met inhibitors in clinical trials[J].Expert Opin Investig Drugs,2011,20(12):1677-1684.
[9]Yap TA,Sandhu SK,Alam SM,et al.HGF/c-MET targeted therapeutics:novel strategies for cancer medicine[J].Curr Drug Targets,2011,12(14):2045-2058.
[10]那彦群,叶章群,孙颖浩.中国泌尿外科疾病诊断治疗指南[M].北京:人民卫生出版社,2014:65-67.
[11]Huang S,Cui H,Lou Z,et al.Association of rs3787016 in long non-coding RNAs POLR2E and rs2910164 in miRNA-146a with prostate cancer:a systematic review and meta-analysis[J].Iran JPublic Health,2018,47(5):623-632.
[12]Hagman Z,Larne O,Edsjo A,et al.MiR-34c is downregulated in prostate cancer and exerts tumor suppressive functions[J].Int JCancer,2010,127(12):2768-2776.
[13]Hagman Z,Haflidadottir BS,Ansari M,et al.The tumour suppressor miR-34c targets MET in prostate cancer cells[J].Br JCancer,2013,109(5):1271-1278.
[14]Li H,Rokavec M,Jiang L,et al.Antagonistic effects of p53 and HIF1A on microRNA-34a regulation of PPP1R11 and STAT3 and hypoxia-induced epithelial to mesenchymal transition in colorectal cancer cells[J].Gastroenterology,2017,153(2):505-520.
[15]Jacobsen F,Ashtiani SN,Tennstedt P,et al.High c-MET expression is frequent but not associated with early PSA recurrence in prostate cancer[J].Exp Ther Med,2013,5(1):102-106.
[16]Kitajima Y,Ide T,Ohtsuka T,et al.Induction of hepatocyte growth factor activator gene expression under hypoxia activates the hepatocyte growth factor/c-Met system via hypoxia inducible factor-1 in pancreatic cancer[J].Cancer Sci,2008,99(7):1341-1347.
[17]Han Y,Luo Y,Zhao J,et al.Overexpression of c-Met increases the tumor invasion of human prostate LNCaP cancer cells in vitro and in vivo[J].Oncol Iett,2014,8(4):1618-1624.
[18]黄远见,肖娟,张志伟,等.miR-34a抑制人鼻咽癌细胞生长与侵袭[J].中南医学科学杂志,2014,42(3):251-254.
[19]Hagman Z,Haflidadottir BS,Ansari M,et al.The tumour suppressor miR-34c targets MET in prostate cancer cells[J].Br JCancer,2013,109(5):1271-1278.
[20]Moumen A,Patane S,Porras A,et al.Met acts on Mdm2 via m TOR to signal cell survival during development[J].Development,2007,134(7):1443-1451.