结直肠癌p53和DNA损伤调节基因1的表达及临床意义

Expression of p53 and DNA damage regulated gene 1 in colorectal cancer and its clinical signifi cance

目的 分析p53和DNA损伤调节基因1(p53 and DNA damage regulated gene 1,PDRG1)在结直肠癌中的表达及其临床意义。方法 检索癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中结直肠癌数据集,比较PDRG1 mRNA在结直肠癌组织和正常结直肠组织中的表达差异,分析其表达与临床病理特征及预后的关系。DNA甲基化交互可视化数据库(DNA methylation interactive visualization database,DNMIVD)分析PDRG1基因甲基化与m RNA表达水平的关系。另选取本院2019年2月至2020年5月存档的102例结直肠癌组织及其癌旁正常结直肠组织石蜡标本进行验证,采用免疫组织化学法检测PDRG1蛋白的表达。结果 TCGA数据库分析发现,PDRG1 mRNA在结直肠癌组织(n=284)中的表达较正常结直肠组织(n=41)增高(P<0.01),且结直肠癌PDRG1 mRNA表达与拷贝数变异呈正相关(n=273;r=0.792,P<0.01)。DNMIVD分析显示,PDRG1启动子甲基化β值与基因表达水平呈负相关(r=-0.34,P<0.01)。TCGA数据库分析显示,结直肠癌患者(n=273)PDRG1 mRNA表达在肿瘤位置、TNM分期及远处转移方面比较,差异均具有统计学意义(均P<0.05);对245例结直肠癌患者进行Kaplan-Meier生存分析发现,PDRG1 mRNA高表达患者(以中位数为分界值,大于中位数为高表达)无瘤生存期较短(P=0.019)。免疫组织化学检测显示,结直肠癌组织中PDRG1蛋白表达阳性率高于正常结直肠癌组织[87.3%(89/102) vs32.4%(33/102),P<0.01]。结论 PDRG1在结直肠癌中高表达,且与肿瘤位置、远处转移和无瘤生存期有关,可能成为结直肠癌潜在的生物标志物。

Objective To analyze the expression and clinical significance of p53 and DNA damage regulated gene 1(PDRG1)in col-orectal cancer(CRC).Methods The PDRG1 mRNA expression in CRC and normal colorectal tissues and its relationship with the clin-icopathalogical features and prognosis was analyzed using the dataset of CRC patients from The Cancer Genome Atlas(TCGA)database.The relationship between PDRG1 methylation and gene expression was analyzed by DNA methylation interactive visualization database(DNMIVD).Immunohistochemistry(IHC)staining was used to validate PDRG1 protein expression in the paraffin embedded CRC and nor-mal paracancerous tissues of 102 patients archived in our hospital from February 2019 to May 2020.Results PDRG1 mRNA expression in CRC tissues(n=284)was significantly higher than that in 41 cases of normal colorectal tissues(P<0.01).The abnormal amplification of PDRG1 was related to copy number variation(n=273;r=0.792,P<0.01).PDRG1 gene expression was negatively correlated with DNA pro-moter methylation(r=-0.34,P<0.01).In TCGA database,PDRG1 mRNA expression was significantly different in CRC patients(n=273)with different tumor location,TNM stage and distant metastasis status(all P<0.05);Kaplan-Meier analysis of 245 CRC patients showed that CRC patients with high PDRG1 mRNA expression(larger than median mRNA level)had shorter disease-free survival time(P=0.019).IHC staining showed that the positive rate of PDRG1 protein expression in CRC tissues was significantly higher than that in normal colorectal tissues [87.3%(89/102) vs 32.4% (33/102), P<0.01]. Conclusions PDRG1 was upregulated in CRC patients and its high expression was closely related to the primary tumor location, distant metastasis, and disease-free survival, which could be used as a potential biomarker for colorectal cancer.