MYBL2在淋巴结阳性前列腺癌组织中的表达及其对雄激素剥夺治疗结局的预测作用

Expression of MYBL2 in lymph node positive prostate cancer and its predictive effect on androgen deprivation therapy

目的:探讨骨髓母细胞增生症病毒癌基因同源样蛋白2(MYBL2)在淋巴结阳性前列腺癌(PCa)组织中的表达及其对雄激素剥夺治疗结局的预测价值。方法:收集80例行根治性前列腺切除术(RP)PCa患者的组织标本,其中27例经病理证实为淋巴结阳性(LNP)并进行辅助性雄激素剥夺治疗(ADT);另外选取36例良性前列腺增生标本作为对照。免疫组织化学染色法检测组织中MYBL2表达阳性率。利用癌症基因组图谱(TCGA)基因芯片数据库PCa数据集进一步验证MYBL2 mRNA的表达及其与患者预后的关系。结果:MYBL2蛋白在PCa组织中的阳性表达率为45.0%(36/80),显著高于良性前列腺增生组织的11.11%(4/36,P<0.001)。PCa组织中MYBL2蛋白表达与淋巴结转移密切相关,LNP-PCa患者组织MYBL2蛋白阳性表达率(63.64%,21/33)高于非LNP-PCa患者(31.91%,15/47,P=0.005)。Kaplan-Meier生存曲线分析结果显示,LNP-PCa中MYBL2阳性表达者无进展生存期(PFS)短于MYBL2阴性表达者(Log-rankχ^(2)=19.135,P<0.001)。单因素和多因素Cox回归分析均证实组织MYBL2蛋白表达是影响患者PFS的独立预测因素(P=0.002)。TCGA和GTEx数据库分析显示,MYBL2 mRNA在PCa组织中的表达水平显著高于正常组织(P<0.001),MYBL2 mRNA高表达PCa患者的PFS明显缩短(P<0.001)。结论:MYBL2蛋白阳性表达率在PCa组织中显著升高,与LNP-PCa患者临床病理特征和预后有关,可作为PCa临床靶向治疗和预后评价的潜在标志物。

Objective:To investigate the expression of myeloblastosis viral oncogene homolog-like 2(MYBL2)in lymph node positive prostate cancer(PCa)and its predictive value for the outcome of androgen deprivation therapy.Methods:Tissue samples from 80 patients with PCa who underwent radical prostatectomy(RP)were collected,among them 27 patients were pathologically confirmed as lymph node positive(LNP)and underwent androgen deprivation therapy(ADT).In addition,36 benign prostate specimens were selected as control.The positive rate of MYBL2 expression in tissues was detected by immunohistochemical staining.The Cancer Genome Atlas(TCGA)gene chip database PCa dataset was used to further verify the expression of MYBL2 mRNA and its relationship with patient prognosis.Results:The positive expression rate of MYBL2 protein in PCa tissues was 45.0%(36/80),which was higher than that in benign prostatic hyperplasia tissues(11.11%,4/36),the difference was statistically significant(χ^(2)=11.171,P<0.001).The expression of MYBL2 protein in PCa tissues was closely related to lymph node metastasis,and the positive expression rate of MYBL2 protein in LNP-PCa patients(63.64%,21/33)was higher than that in non-LNP-PCa patients(31.91%,15/47,P=0.005).Kaplan-Meier survival curve analysis showed that the progression-free survival(PFS)of MYBL2-positive patients in LNP-PCa was shorter than that of MYBL2-negative patients(Log-rankχ^(2)=19.135,P<0.001).Univariate and multivariate Cox regression analysis showed that tissue MYBL2 protein expression was an independent predictor of PFS(P=0.002).Analysis of the TCGA and GTEx databases showed that the expression level of MYBL2 mRNA in PCa tissues was significantly higher than that in normal tissues(P<0.001),and PFS in PCa patients with high expression of MYBL2 mRNA was significantly shortened(P<0.001).Conclusion:The positive expression rate of MYBL2 protein is significantly increased in PCa tissues,which is related to the clinicopathological characteristics and prognosis of LNP-PCa patients.MYBL2 can be used as a potential marker for clinical targeted therapy and prognosis evaluation of PCa.