乳腺癌中PRDM2、PRDM5、PRDM16的甲基化检测及临床意义
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摘要
目的探讨乳腺癌中PR锌指区域蛋白(PRDM) 2、PRDM5、PRDM16的甲基化检测及临床意义。方法回顾性选取沧州市中心医院收集74例乳腺癌患者组织作为乳腺癌组,另选取62例乳腺良性肿瘤患者组织作为对照组。采用甲基化特异性聚合酶链反应(MSP)检测PRDM2、PRDM5、PRDM16甲基化情况,并分析其与乳腺癌患者临床病理参数的关系,采用COX风险回归对乳腺癌患者无生存进展期(PFS)、总体生存时间(OS)的影响因素进行分析,KaplanMeier法分析患者3年预后情况。结果乳腺癌组织中PRDM2、PRDM5、PRDM16基因启动子甲基化阳性率显著均高于对照组,差异有统计学意义(P <0. 05)。PRDM2、PRDM5启动子甲基化与TNM分期、淋巴结转移、组织学分级相关,PRDM16启动子甲基化与TNM分期、淋巴结转移相关,差异有统计学意义(P <0. 05)。COX风险回归分析显示,PRDM2、PRDM5、PRDM16启动子甲基化是乳腺癌患者PFS、OS的独立影响因素。乳腺癌患者PRDM2、PRDM5、PRDM16启动子甲基化者PFS、OS均低于未甲基化者,差异有统计学意义(P <0. 05)。结论乳腺癌患者PRDM2、PRDM5、PRDM16启动子甲基化在乳腺癌的病情进展中发挥着重要作用,与患者预后相关,可作为其预后检测指标。
Objective The methylation detection of PR zinc finger region protein-2( PRDM2),PRDM5 and PRDM16 in breast cancer and its clinical significance. Methods Seventy-four cases tissues of breast cancer patients in our hospital were selected as breast cancer group,another sixty-two cases of patients with benign breast tumor were selected as control group,methylation specific polymerase chain reaction( MSP) was used to detect the methylation of PRDM2,PRDM5 and PRDM16,its relationship with clinicopathological parameters in in breast cancer patients was analyzed,COX risk regression was used to analyze the progression free survival( PFS) and overall survival time( OS) of breast cancer patients,Kaplan-Meier analyzed the prognosis after three years. Results The positive rates of PRDM2,PRDM5 and PRDM16 gene promoter methylation in breast cancer tissues were significantly higher than those in control group,the difference was statistically significant( P < 0. 05). Methylation of PRDM2 and PRDM5 promoter were associated with TNM stage,lymph node metastasis and histological grade. The methylation of PRDM16 promoter were associated with TNM stage and lymph node metastasis,and the difference was statistically significant( P < 0. 05). COX risk regression analysis showed that methylation of PRDM2,PRDM5 and PRDM16 promoter was an independent prognostic factors for PFS and OS in breast cancer patients.The PFS and OS levels in breast cancer patients with PRDM2,PRDM5 and PRDM16 promoter methylation were lower than those with non methylation,and the differences were statistically significant( P < 0. 05). Conclusion Methylation of PRDM2,PRDM5 and PRDM16 promoter plays an important role in the progression of breast cancer,and is related to the prognosis,and can be used as a prognostic indicator.
Objective The methylation detection of PR zinc finger region protein-2( PRDM2),PRDM5 and PRDM16 in breast cancer and its clinical significance. Methods Seventy-four cases tissues of breast cancer patients in our hospital were selected as breast cancer group,another sixty-two cases of patients with benign breast tumor were selected as control group,methylation specific polymerase chain reaction( MSP) was used to detect the methylation of PRDM2,PRDM5 and PRDM16,its relationship with clinicopathological parameters in in breast cancer patients was analyzed,COX risk regression was used to analyze the progression free survival( PFS) and overall survival time( OS) of breast cancer patients,Kaplan-Meier analyzed the prognosis after three years. Results The positive rates of PRDM2,PRDM5 and PRDM16 gene promoter methylation in breast cancer tissues were significantly higher than those in control group,the difference was statistically significant( P < 0. 05). Methylation of PRDM2 and PRDM5 promoter were associated with TNM stage,lymph node metastasis and histological grade. The methylation of PRDM16 promoter were associated with TNM stage and lymph node metastasis,and the difference was statistically significant( P < 0. 05). COX risk regression analysis showed that methylation of PRDM2,PRDM5 and PRDM16 promoter was an independent prognostic factors for PFS and OS in breast cancer patients.The PFS and OS levels in breast cancer patients with PRDM2,PRDM5 and PRDM16 promoter methylation were lower than those with non methylation,and the differences were statistically significant( P < 0. 05). Conclusion Methylation of PRDM2,PRDM5 and PRDM16 promoter plays an important role in the progression of breast cancer,and is related to the prognosis,and can be used as a prognostic indicator.
引文
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[9] Kim JH,Dhanasekaran SM,Prensner JR,et al. Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer[J]. Genome Res,2016,21(7):1028-1041.
[10] Ellis RJ,Wang Y,Stevenson HS,et al. Genome-wide methylation patterns in papillary thyroid cancer are distinct based on histological subtype and tumor genotype[J]. J Clin Endocrinol Metab,2014,99(2):329-337.
[11] Qi LN,Li LQ,Chen YY,et al. Genome-wide and differential proteomic analysis of hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma in Guangxi,China[J]. Plos One,2013,8(12):83465-83472.
[12] Song W,Zhao Y,Rui Y,et al. Novel variants inMLLconfer to bladder cancer recurrence identified by whole-exome sequencing[J]. Oncotarget,2016,7(3):2629-2645.
[13]王洋,夏梓元,黄美金,等. PRDM5基因抑制前列腺癌细胞22Rv1生长[J].第二军医大学学报,2016,37(6):724-728.
[14] Galli GG,Carrara M,Francavilla C,et al. Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells[J]. Mol Cell Biol,2013,33(22):4504-16.
[15] Galli GG,Multhaupt HA,Carrara M,et al. Prdm5 suppresses ApcMin-driven intestinal adenomas and regulates monoacylglycerol lipase expression[J]. Oncogene,2014,33(25):3342-3348.
[16] Cheng HY,Chen XW,Cheng L,et al. DNA methylation and carcinogenesis of PRDM5 in cervical cancer[J]. J Cancer Res Clin Oncol,2010,136(12):1821-1825.
[17] Cheedipudi S,Gala HP,Puri D,et al. Identification of PRDM2 regulated genes in quiescent C2C12 myoblasts[J]. Genomics Data,2015,6(1-2):264.
[18] Sonnet M,Claus R,Becker N,et al. Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia[J]. Genome Med,2014,6(4):34-42.
[19] Tan SX,Hu RC,Liu JJ,et al. Methylation of PRDM2,PRDM5 and PRDM16 genes in lung cancer cells[J]. Int J Clin Exp Pathol,2014,7(5):2305-2311.
[2]李少英,李荣,荣磊,等.乳腺癌患者外周血DNA中PTPRO基因甲基化异常的检测及其临床意义[J].肿瘤,2013,33(12):1087-1094.
[3]李怡晓,李锋,张娜,等. Jagged1基因甲基化与乳腺癌发生发展相关性探讨[J].中华肿瘤防治杂志,2015,22(11):846-850.
[4]谭永丽,谭双香,胡瑞成,等. PRDM基因及DNA甲基化与肿瘤关系的研究进展[J].国际肿瘤学杂志,2013,40(3):174-176.
[5] Escobar PF,Patrick RJ,Rybicki LA,et al. The 2003 revised TNM staging system for breast cancer:results of stage re-classification on survival and future comparisons among stage groups[J]. Ann Surg Oncol,2007,14(1):143-147.
[6]张兴艳,马志萍,崔文丽,等.弥漫性大B细胞淋巴瘤中PRDM 1基因甲基化状态与预后的相关性[J].中华病理学杂志,2016,45(12):831-837.
[7] Di Zazzo E,De Rosa C,Abbondanza C,et al. PRDM Proteins:Molecular Mechanisms in Signal Transduction and Transcriptional Regulation[J]. Biology,2013,2(1):107-141.
[8] Zhou B,Wang J,Lee S Y,et al. PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity[J]. Mol Cell,2016,62(2):222-236.
[9] Kim JH,Dhanasekaran SM,Prensner JR,et al. Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer[J]. Genome Res,2016,21(7):1028-1041.
[10] Ellis RJ,Wang Y,Stevenson HS,et al. Genome-wide methylation patterns in papillary thyroid cancer are distinct based on histological subtype and tumor genotype[J]. J Clin Endocrinol Metab,2014,99(2):329-337.
[11] Qi LN,Li LQ,Chen YY,et al. Genome-wide and differential proteomic analysis of hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma in Guangxi,China[J]. Plos One,2013,8(12):83465-83472.
[12] Song W,Zhao Y,Rui Y,et al. Novel variants inMLLconfer to bladder cancer recurrence identified by whole-exome sequencing[J]. Oncotarget,2016,7(3):2629-2645.
[13]王洋,夏梓元,黄美金,等. PRDM5基因抑制前列腺癌细胞22Rv1生长[J].第二军医大学学报,2016,37(6):724-728.
[14] Galli GG,Carrara M,Francavilla C,et al. Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells[J]. Mol Cell Biol,2013,33(22):4504-16.
[15] Galli GG,Multhaupt HA,Carrara M,et al. Prdm5 suppresses ApcMin-driven intestinal adenomas and regulates monoacylglycerol lipase expression[J]. Oncogene,2014,33(25):3342-3348.
[16] Cheng HY,Chen XW,Cheng L,et al. DNA methylation and carcinogenesis of PRDM5 in cervical cancer[J]. J Cancer Res Clin Oncol,2010,136(12):1821-1825.
[17] Cheedipudi S,Gala HP,Puri D,et al. Identification of PRDM2 regulated genes in quiescent C2C12 myoblasts[J]. Genomics Data,2015,6(1-2):264.
[18] Sonnet M,Claus R,Becker N,et al. Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia[J]. Genome Med,2014,6(4):34-42.
[19] Tan SX,Hu RC,Liu JJ,et al. Methylation of PRDM2,PRDM5 and PRDM16 genes in lung cancer cells[J]. Int J Clin Exp Pathol,2014,7(5):2305-2311.
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