乳腺癌中血浆游离DNA含量和完整性的临床应用
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摘要
目的探讨血浆循环游离脱氧核糖核酸(cf DNA)含量和完整性在乳腺癌诊断和预后监测中的临床意义。方法收集106例初诊乳腺癌患者血浆标本、72例乳腺良性腺病患者及301名体检健康者血浆标本,提取cf DNA,实时荧光定量聚合酶链反应(PCR)检测cf DNA中100 bp和241 bp长度的人端粒酶逆转录酶(h TERT)的含量,计算cf DNA完整性,分析3个组间差异及与肿瘤负荷的关系。应用受试者工作特征(ROC)曲线,分析100 bp和241 bp h TERT含量及完整性对乳腺癌诊断的灵敏度和特异度。结果 100 bp和241 bp h TERT含量在乳腺癌患者中明显高于乳腺良性腺病患者和体检健康者,差异有统计学意义(P<0.001),完整性与淋巴结转移相关(P<0.01)。ROC曲线表明100 bp、241 bp h TERT含量及完整性的曲线下面积(AUC)分别是0.693、0.792、0.865;三者敏感度分别为73.3%、68.0%、66.7%,特异度分别为68%、80%、92%。结论 cf DNA含量和完整性的检测在乳腺癌的诊疗中有一定临床价值,可作为乳腺癌诊断和预后监测的指标。
Objective To investigate the roles of plasma cell-free deoxyribonucleic acid(cf DNA)levels and its integrity in the diagnosis and prognosis of breast cancer. Methods Plasma samples were collected from 106 patients newly diagnosed as breast cancer,72 breast benign disease patients and 301 healthy subjects. Plasma cf DNA was extracted,and then 100 bp and 241 bp human telomerase reverse transcriptases(h TERT)were quantified by real-time fluorescence quantitation polymerase chain reaction(PCR). The cf DNA integrity was calculated,and the difference among the 3 groups and the relationship with tumor burden were analyzed. The sensitivities and specificities of 100 bp and 241 bp h TERT levels and cf DNA integrity for the diagnosis of breast cancer were evaluated by receiver operating characteristic(ROC)curve. Results The levels of 100 bp and 241 bp h TERT in breast cancer patients were higher than those in breast benign disease patients and healthy subjects(P<0.001). The integrity of cf DNA was related to lymph node metastasis(P<0.01). The areas under ROC curves(AUC)of 100 bp and 241 bp h TERT levels and cf DNA integrity were 0.693,0.792 and 0.865. The sensitivities were 73.3%,68.0% and 66.7%,and the specificities were 68%,80% and 92%,respectively. Conclusions The determinations of cf DNA levels and its integrity have certain clinical significance in the diagnosis and treatment of breast cancer,which could be as tumor biomarkers for the diagnosis and prognosis of breast cancer.
Objective To investigate the roles of plasma cell-free deoxyribonucleic acid(cf DNA)levels and its integrity in the diagnosis and prognosis of breast cancer. Methods Plasma samples were collected from 106 patients newly diagnosed as breast cancer,72 breast benign disease patients and 301 healthy subjects. Plasma cf DNA was extracted,and then 100 bp and 241 bp human telomerase reverse transcriptases(h TERT)were quantified by real-time fluorescence quantitation polymerase chain reaction(PCR). The cf DNA integrity was calculated,and the difference among the 3 groups and the relationship with tumor burden were analyzed. The sensitivities and specificities of 100 bp and 241 bp h TERT levels and cf DNA integrity for the diagnosis of breast cancer were evaluated by receiver operating characteristic(ROC)curve. Results The levels of 100 bp and 241 bp h TERT in breast cancer patients were higher than those in breast benign disease patients and healthy subjects(P<0.001). The integrity of cf DNA was related to lymph node metastasis(P<0.01). The areas under ROC curves(AUC)of 100 bp and 241 bp h TERT levels and cf DNA integrity were 0.693,0.792 and 0.865. The sensitivities were 73.3%,68.0% and 66.7%,and the specificities were 68%,80% and 92%,respectively. Conclusions The determinations of cf DNA levels and its integrity have certain clinical significance in the diagnosis and treatment of breast cancer,which could be as tumor biomarkers for the diagnosis and prognosis of breast cancer.
引文
[1]魏旭倩,王伟祥,王学锋,等.外周血C EAmRNA、Survivin mRNA、MMP-2 mRNA和TIMP-2 mRNA水平与乳腺癌的关系[J].检验医学,2011,26(2):94-99.
[2]PATHAK A K,BHUTANI M,KUMAR S,et al.Circulating cell-free DNA in plasma/serum of lung cancer patients as a potential screening and prognostic tool[J].Clin Chem,2006,52(10):1833-1842.
[3]JIN Z,EL-DEIRY W S.Overview of cell death signaling pathways[J].Cancer Biol Ther,2005,4(2):139-163.
[4]WANG B G,HUANG H Y,CHEN Y C,et al.Increased plasma DNA integrity in cancer patients[J].Cancer Res,2003,63(14):3966-3968.
[5]杨英俊,黄平,李程华,等.肝细胞癌患者血浆hTERT DNA的检测及其临床意义[J].临床检验杂志,2011,29(4):260-262.
[6]郁佳佳,施维,鞠少卿.循环游离DNA完整性检测的临床应用研究进展[J].临床检验杂志,2013,31(2):121-123.
[7]DAWSON S J,TSUI D W,MURTAZA Met al.Analysis of circulating tumor DNA to monitor metastatic breast cancer[J].N Engl J Med,2013,368(13):1199-1209.
[8]BREITBACH S,TUG S,SIMON[8]P.Circulating cell-free DNA:an up-coming molecular marker in exercise physiology[J].Sports Med,2012,42(7):565-586.
[9]NAGATA S,HANAYAMA R,KAWANE K.Autoimmunity and the clearance of dead cells[J].Cell,2010,140(5):619-630.
[10]庞达,夏冰舒,张显玉.循环游离DNA在乳腺癌中的临床应用[J].中国肿瘤临床,2015,53(5):261-264.
[11]ALIX-PANABIERES C,SCHWARZENBACH H,PANTEL K.Circulating tumor cells and circulating tumor DNA[J].Annu Rev Med,2012,63:199-215.
[12]ULIVI P,SIVESTRINI R.Role of quantitative and qualitative characteristics of free circulating DNA in the management of patients with non-small cell lung cancer[J].Cell Oncol(Dordr),2013,36(6):439-448.
[13]LIANG D H,ENSOR J E,LIU Z B,et al.Cellfree DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients[J].Breast Cancer Res Treat,2016,155(1):139-149.
[14]黄宝丽,李翔翔,王琳,等.非小细胞肺癌患者血浆游离DNA含量和完整性检测的临床意义[J].临床检验杂志,2015,33(8):602-605.
[15]RYKOVA E Y,TSVETOVSKAYA G A,SERGEEVA G I,et al.Methylation-based analysis of circulating DNA for breast tumor screening[J].Ann N Y Acad Sci,2008,1137:232-235.
[16]关婷,叶长烂,张宏斌,等.宫颈癌患者血浆游离DNA的含量变化研究[J].实用诊断与治疗杂志,2008,22(8):576-578.
[17]UMETANI N,GIULIANO A E,HIRAMATSU S H,et al.Prediction of breast tumor progression by integrity of free circulating DNA in serum[J].J Clin Oncol,2006,24(26):4270-4276.
[18]IQBAL S,VISHNUBHATLA S,RAINA V,et al.Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer[J].Springerplus,2015,4:265.
[19]STZER O J,LEHNER J,FERSCHINGGIERLICHD,et al.Diagnostic relevance of plasma DNA and DNA integrity for breast cancer[J].Tumour Biol,2014,35(2):1183-1191.
[2]PATHAK A K,BHUTANI M,KUMAR S,et al.Circulating cell-free DNA in plasma/serum of lung cancer patients as a potential screening and prognostic tool[J].Clin Chem,2006,52(10):1833-1842.
[3]JIN Z,EL-DEIRY W S.Overview of cell death signaling pathways[J].Cancer Biol Ther,2005,4(2):139-163.
[4]WANG B G,HUANG H Y,CHEN Y C,et al.Increased plasma DNA integrity in cancer patients[J].Cancer Res,2003,63(14):3966-3968.
[5]杨英俊,黄平,李程华,等.肝细胞癌患者血浆hTERT DNA的检测及其临床意义[J].临床检验杂志,2011,29(4):260-262.
[6]郁佳佳,施维,鞠少卿.循环游离DNA完整性检测的临床应用研究进展[J].临床检验杂志,2013,31(2):121-123.
[7]DAWSON S J,TSUI D W,MURTAZA Met al.Analysis of circulating tumor DNA to monitor metastatic breast cancer[J].N Engl J Med,2013,368(13):1199-1209.
[8]BREITBACH S,TUG S,SIMON[8]P.Circulating cell-free DNA:an up-coming molecular marker in exercise physiology[J].Sports Med,2012,42(7):565-586.
[9]NAGATA S,HANAYAMA R,KAWANE K.Autoimmunity and the clearance of dead cells[J].Cell,2010,140(5):619-630.
[10]庞达,夏冰舒,张显玉.循环游离DNA在乳腺癌中的临床应用[J].中国肿瘤临床,2015,53(5):261-264.
[11]ALIX-PANABIERES C,SCHWARZENBACH H,PANTEL K.Circulating tumor cells and circulating tumor DNA[J].Annu Rev Med,2012,63:199-215.
[12]ULIVI P,SIVESTRINI R.Role of quantitative and qualitative characteristics of free circulating DNA in the management of patients with non-small cell lung cancer[J].Cell Oncol(Dordr),2013,36(6):439-448.
[13]LIANG D H,ENSOR J E,LIU Z B,et al.Cellfree DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients[J].Breast Cancer Res Treat,2016,155(1):139-149.
[14]黄宝丽,李翔翔,王琳,等.非小细胞肺癌患者血浆游离DNA含量和完整性检测的临床意义[J].临床检验杂志,2015,33(8):602-605.
[15]RYKOVA E Y,TSVETOVSKAYA G A,SERGEEVA G I,et al.Methylation-based analysis of circulating DNA for breast tumor screening[J].Ann N Y Acad Sci,2008,1137:232-235.
[16]关婷,叶长烂,张宏斌,等.宫颈癌患者血浆游离DNA的含量变化研究[J].实用诊断与治疗杂志,2008,22(8):576-578.
[17]UMETANI N,GIULIANO A E,HIRAMATSU S H,et al.Prediction of breast tumor progression by integrity of free circulating DNA in serum[J].J Clin Oncol,2006,24(26):4270-4276.
[18]IQBAL S,VISHNUBHATLA S,RAINA V,et al.Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer[J].Springerplus,2015,4:265.
[19]STZER O J,LEHNER J,FERSCHINGGIERLICHD,et al.Diagnostic relevance of plasma DNA and DNA integrity for breast cancer[J].Tumour Biol,2014,35(2):1183-1191.