前列腺癌组织肝激酶B1,Rab鸟嘌呤核苷酸交换因子-5 mRNA表达水平与临床病理特征和预后的相关性研究

Correlation between the Expression Levels of Liver Kinase B1,Rab Guanine Nucleotide Exchange Factor-5 mRNA in Prostate Cancer Tissues and Its Clinicopathological Characteristics and Prognosis

目的研究前列腺癌患者癌组织中肝激酶B1(liver kinase B1,LKB1)及Rab鸟嘌呤核苷酸交换因子-5(Rab guanine nucleotide exchage factor-5,Rab EX-5)mRNA表达及临床意义。方法应用实时荧光定量PCR(qRT-PCR)检测92例前列腺癌组织和80例良性前列腺增生组织中LKB1及RabEX-5 mRNA的表达,比较LKB1,RabEX-5 mRNA表达组间差异及与临床病理特征的关系。Pearson线性相关分析LKB1与RabEX-5 mRNA表达的相关性。Kaplan-Meier生存分析LKB1,RabEX-5 mRNA表达与前列腺癌患者生存预后的关系。多因素COX回归分析影响前列腺癌患者生存预后的危险因素。结果与前列腺增生组织相比,前列腺癌组织中RabEX-5 mRNA表达明显升高(1.311±0.374 vs 0.457±0.083),差异有统计学意义(t=20.758,P=0.000),而LKB1 mRNA表达显著降低(0.373±0.052 vs 1.234±0.268),差异有统计学意义(t=30.181,P=0.000)。LKB1,RabEX-5 mRNA表达与Gleason评分、骨转移、TNM分期有关(t=2.419~9.965,均P<0.05),与年龄、前列腺特异抗原(PSA)水平无关(t=0.379~1.453,均P>0.05)。前列腺癌组织中LKB1与RabEX-5 mRNA的表达呈显著负相关(r=-0.402,P=0.000)。低LKB1表达组3年总体生存率低于高LKB1表达组(χ^(2)=55.605,P=0.000),高RabEX-5表达组3年总体生存率低于低RabEX-5表达组(χ^(2)=29.435,P=0.000)。多因素COX回归分析结果表明,Gleason评分≥7分(OR=2.671,P=0.018)、骨转移(OR=1.528,P=0.031)、TNM分期为Ⅲ期(OR=1.634,P=0.037),LKB1 mRNA低表达(OR=1.764,P=0.008)及RabEX-5 mRNA高表达(OR=2.587,P=0.000)是影响前列腺癌患者生存预后的危险因素(P<0.05)。结论前列腺癌组织中RabEX-5 mRNA表达升高,而LKB1 mRNA表达降低,二者共同参与前列腺癌的发生发展,有望成为评估前列腺癌患者预后的组织肿瘤标志物。

Objective To study the expression and clinical significance of liver kinase B1(LKB1)and Rab guanine nucleotide exchange factor-5(RabEX-5)mRNA in cancer tissues of prostate cancer patients.Methods Quantitative real-time PCR(qRTPCR)was used to detect the expression of LKB1 and RabEX-5 mRNA in 92 cases of prostate cancer tissues and 80 cases of benign prostatic hyperplasia tissues.LKB1 and RabEX-5 mRNA expression differences between groups and their relationship with clinicopathological characteristics were compared.Pearson linear correlation analysis was used to analyze the correlation between LKB1 and RabEX-5 mRNA expression.Kaplan-Meier survival analysis were used to analyze the relationship between LKB1 and RabEX-5 expression and the survival prognosis of prostate cancer patients.Multivariate COX regression analysis was used to analyze the risk factors affecting the survival and prognosis of prostate cancer patients.Results Compared with prostatic hyperplasia tissues,the expression of RabEX-5 mRNA in prostate cancer tissue was significantly increased(1.311±0.374 vs 1.457±0.083),the difference was statisticall significant(t=20.758,P=0.000),while the expression of LKB1 mRNA was significantly decreased(0.373±0.052 vs 1.234±0.268),the difference was statistically significant(t=30.181,P=0.000).The expression of LKB1 and RabEX-5 mRNA were related to Gleason score,bone metastasis and TNM stage(t=2.419~9.965,all P<0.05),but not with age or prostate specific antigen(PSA)level(t=0.379~1.453,all P>0.05).The expression of LKB1 and RabEX-5 mRNA in prostate cancer tissue was significantly negatively correlated(r=-0.402 P=0.000).The 3-year overall survival rate of the low LKB1 expression group was lower than that of the high LKB1 expression group(χ^(2)=55.605,P=0.000),and the 3-year overall survival rate of the high RabEX-5 expression group was lower than that of the low RabEX-5 expression group(χ^(2)=29.435,P=0.000).Multivariate Cox regression analysis showed that Gleason score≥7 scores(OR=2.671,P=0.018),bone metastasis(OR=1.528,P=0.031),TNM stageⅢ(OR=1.634,P=0.037),low expression of LKB1 mRNA(OR=1.764,P=0.008)and high expression of RabEX-5mRNA(OR=2.587,P=0.000)were risk factors affecting the survival prognosis of prostate cancer patients(P<0.05).Conclusion RabEX-5 mRNA expression was increased in prostate cancer tissues,while LKB1 mRNA expression is decreased.The two were jointly involved in the occurrence and development of prostate cancer.They are expected to become tissue tumor markers that indicate the prognosis of prostate cancer patients.