DMBT1基因在前列腺癌中表达的显著下调及临床意义

The low expression of DMBT1 gene in prostate cancer and its clinical significance

目的研究前列腺癌发生过程中可能受甲基化调节的基因,检测其在前列腺癌细胞系和组织中的表达并分析其表达水平与临床病理特征的关系。方法采用人类全基因表达谱芯片筛选出可能因去甲基化导致恢复表达的基因后,以实时荧光定量PCR检测其在前列腺癌细胞系LNCaP、PC-3及39例前列腺癌和16例前列腺正常组织中mRNA的表达情况。Western blot检测以上标本中目的蛋白的表达水平。结果在用甲基化抑制剂处理后,PC-3细胞系中DMBT1(deleted in malignant braintumor)基因表达显著上调,而在LNCaP细胞系中未见到显著改变。在100%的前列腺癌患者组织中DMBT1 mRNA及蛋白表达均显著下调。统计分析表明,DMBT1 mRNA的表达水平与cTNM分期及骨转移有关,而与年龄、PSA水平及肿瘤分化程度无显著关系。结论 DMBT1有可能成为指导前列腺癌分期及判断预后的分子标志物。但DMBT1的调控机制以及DMBT1在细胞生理和肿瘤发生中的作用还需要进一步的研究。

Objective To identify the genes that might be regulated by methylation during the prostate tumorigenesis,detect the expression of the genes in prostate cancer cell lines and tissues,and evaluate the potential correlation between the gene expressions and clinical/pathologic features.Methods We used the Whole Human Genome Oligo Microarray to screen the treated cells and the controlled groups to identify the genes which restored expression after anti-methylation.Then we detected the expressions of DMBT1 in mRNA and protein levels by real-time quantitative PCR and western blot in prostate cancer cell lines（LNCaP PC-3） and prostatic tissues from 16 benign lesions and 39 carcinomas.Results The expression of DMBT1 gene（Deleted in Malignant Brain Tumor） was significantly up-regulated in treated PC-3 cell lines than in controlled cell lines;however,no similar expression change was observed in treated or controlled LNCaP cell lines.Compared to the normal prostatic tissues,mRNA and protein expressions of DMBT1 gene were significantly down-regulated in whole prostate cancer tissue samples.The statistical results showed that the expressions of DMBT1 were correlated to clinical stage and osseous metastasis,but not to patient age,PSA level and tumor grades.Conclusions The DMBT1 gene is confirmed to be a potential biomarker in identifying hormonal independent subgroup from hormonal dependent prostatic carcinomas,as well as the prognostic value with its correlation to clinical stage and tumor grades.It is necessary to elucidate the regulation mechanism of DMBT1 and its contribution in cell physiology and tumorigenesis.