MTA2对前列腺癌预后的预测价值及在癌转移过程中的作用

The predictive value of metastasis-associated protein 2 in the prognosis of prostate cancer and its role in cancer metastasis

目的探讨转移相关蛋白2(MTA2)对前列腺癌预后的预测价值及在癌转移过程中的作用。方法收集空军军医大学第一附属医院2018年1月~2020年6月收治的50例前列腺癌患者的癌组织及配对癌旁组织样本用于免疫组织化学分析。根据MTA2蛋白的表达水平将样本分为两组,染色评分≥4为高表达组,<4为低表达组。对人前列腺癌细胞系(PC-3)转染shMTA2(MTA2-shRNA-pLKO.1)来沉默MTA2作为shMTA2组,转染Luc-shRNA-pLKO.1的细胞作为阴性对照组(shNC组),未转染的细胞作为空白对照组(control组)。通过MTT法检测细胞活力,Transwells实验进行体外迁移和侵袭分析。通过qRT-PCR或Western Blot检测细胞中MTA2、Eotaxin-1、CCR3、p-ERK1/2、t-ERK1/2和MMP-3的表达。结果前列腺癌组织中MTA2的染色评分显著高于癌旁组织(5.16±0.87 vs 2.34±0.39,t=9.221,P<0.001)。低表达组患者中出现淋巴结转移率为14.29%(2/14),高表达组患者中出现淋巴结转移率为52.78%(19/36),两组比较差异有统计学意义(χ^(2)=6.131,P=0.013)。与低表达组相比,高表达组患者的生存时间更长(χ^(2)=4.756,P=0.029)。与空白对照组相比,shMTA2组的细胞活力降低了56.87%(P<0.001),细胞迁移数量降低了65.80%(P<0.001),细胞侵袭数量降低了56.35%(P<0.001),Eotaxin-1、CCR3、p-ERK1/2和MMP-3的蛋白相对表达量依次降低了76.03%、69.12%、72.32%和54.67%(P<0.001)。结论前列腺癌组织中MTA2的表达水平升高且与患者的预后有关,沉默MTA2可降低前列腺癌细胞的迁移和侵袭能力,并抑制Eotaxin-CCR3-ERK1/2-MMP-3轴。

Objective To reveal the predictive value of metastasis-associated protein 2(MTA2)on the prognosis of prostate cancer and its role in the process of cancer metastasis.Methods From January 2018 to June 2020,a total of 50 prostate cancer tissues and paired adjacent tissue samples of The First Affiliated Hospital of Air Force Medical University were collected for immunohistochemical analysis.The samples were divided into two groups according to the expression of MTA2 protein.The staining score≥4 was high expression,and<4 was low expression.Human prostate cancer cell line(PC-3)was transfected with shMTA2(MTA2-shRNA-pLKO.1)to silence MTA2,shNC(Luc-shRNA-pLKO.1)was used as a negative control,and untransfected cells were used as a blank control(Control).Cell viability was detected by the MTT method,and the Transwells experiment was used for in vitro migration and invasion analysis.The expression of MTA2,Eotaxin-1,CCR3,p-ERK1/2,t-ERK1/2 and MMP-3 in cells was detected by qRT-PCR or Western Blot.Results The staining score of MTA2 in prostate cancer tissue was significantly higher than that in adjacent tissues(5.16±0.87 vs 2.34±0.39,t=9.221,P<0.001).There were significant differences in lymph node metastasis between the two groups.14.29%(2/14)of patients with low MTA2 expression had lymph node metastasis,and 52.78%(19/36)of patients with high MTA2 expression had lymph node metastasis(χ^(2)=6.131,P=0.013).The survival time of patients with low and high expression of MTA2 was significantly different(χ^(2)=4.756,P=0.029).Compared with the control group,the cell viability of the shMTA2 group was reduced by 56.87%(P<0.001),the number of cell migration was reduced by 65.80%(P<0.001),the number of cell invasion was reduced by 56.35%(P<0.001),the relative protein expression of Eotaxin-1,CCR3,p-ERK1/2 and MMP-3 decreased by 76.03%,69.12%,72.32%and 54.67%respectively(P<0.001),while the relative protein expression of t-ERK1/2 did not change significantly(P>0.05).Conclusion The expression level of MTA2 in prostate cancer tissue is elevated and is related to the prognosis of the patient,silencing MTA2 can reduce the migration and invasion of prostate cancer cells,and inhibit the Eotaxin-CCR3-ERK1/2-MMP-3 axis.