ERG相关融合基因在前列腺癌早期诊断中的应用
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摘要
目的探讨E26(E-Twenty six,ETS)相关融合基因(ETS-related gene,ERG)在前列腺癌早期诊断与淋巴结转移预测中的应用价值。方法选择2010年5月至2016年5月深圳市宝安区中心医院收治的怀疑为前列腺癌而接受前列腺活检的67例患者为研究对象。所有患者均进行ERG相关融合基因表达检测和组织病理学检查,分析影响前列腺癌发生以及淋巴结转移的危险因素。结果 67例患者中,59例患者经过组织病理学检查明确为前列腺癌,8例患者经过组织病理学检查明确为前列腺良性病变。从59例前列腺癌患者中随机抽取8例,与8例确诊为前列腺良性病变者共同测定ERG相关融合基因表达情况。其中,前列腺癌组ERG相关融合基因阳性表达率为75.0%,前列腺良性病变组ERG相关融合基因阳性表达率为25.0%,其差异具有统计学意义(P<0.05);单因素分析显示,患者年龄、前列腺特异性抗原(prostate cancer specific antigen,PSA)水平、PSA速率、ERG相关融合基因是导致前列腺癌发生的高危因素(P<0.05);多因素回归分析显示,PSA速率和ERG相关融合基因是导致前列腺癌发生的独立危险因素(P<0.05);59例前列腺癌患者均进行手术治疗,术中发现淋巴结转移27例,非淋巴结转移32例,前列腺癌淋巴结转移诊断的ERG相关融合基因畸变率阈值为2.6%,ERG相关融合基因诊断前列腺癌淋巴结转移的ROC曲线下面积为0.820,高于PSA的ROC曲线下面积0.718,ERG相关融合基因诊断前列腺癌淋巴结转移的效能显著优于PSA(P<0.05)。结论 ERG相关融合基因阳性表达可以作为前列腺癌发生的辅助评估工具,且对前列腺癌淋巴结转移具有预测价值。
Objective To investigate the effect of E26-related gene(ERG) in the early diagnosis of prostate cancer and the prediction of lymph node metastasis. Method 67 suspected patients underwent prostate biopsy in Baoan District Central Hospital from May 2010 to May 2016 were selected. All the patients underwent detection of the expression of ERG and histopathological examination to analyze the risk factors of lymph node metastasis and prostate cancer. Results Among the 67 suspected patients, 59 ones were confirmed with prostate cancer and 8 cases were confirmed with benign prostatic lesions by histopathological examination. Another 8 cases were randomly selected from the 59 patients with prostate cancer to detect the expression of ERG together with the 8 cases with benign prostatic lesions. The positive expression rate of ERG in prostate cancer group(75.0%) was higher than that in the benign prostatic lesion group(25.0%), with statistically significant difference(P<0.05). According to univariate analysis, age, prostate specific antigen(PSA) level, PSA rate and ERG were all the risk factors for prostate cancer(P<0.05). According to multivariate regression analysis, PSA rate and ERG were independent risk factors for prostate cancer(P<0.05). All the 59 patients with prostate cancer underwent surgical treatment, where lymph node metastasis was found in 27 cases. The aberration rate threshold of ERG was 2.6% and the area under the ROC curve was 0.820, larger than that of the PSA(0.718), with statistically significant difference(P<0.05). Conclusions The positive expression of ERG can serve as an auxiliary assessment tool of prostate cancer, which is also of predictive value for lymph node metastasis.
Objective To investigate the effect of E26-related gene(ERG) in the early diagnosis of prostate cancer and the prediction of lymph node metastasis. Method 67 suspected patients underwent prostate biopsy in Baoan District Central Hospital from May 2010 to May 2016 were selected. All the patients underwent detection of the expression of ERG and histopathological examination to analyze the risk factors of lymph node metastasis and prostate cancer. Results Among the 67 suspected patients, 59 ones were confirmed with prostate cancer and 8 cases were confirmed with benign prostatic lesions by histopathological examination. Another 8 cases were randomly selected from the 59 patients with prostate cancer to detect the expression of ERG together with the 8 cases with benign prostatic lesions. The positive expression rate of ERG in prostate cancer group(75.0%) was higher than that in the benign prostatic lesion group(25.0%), with statistically significant difference(P<0.05). According to univariate analysis, age, prostate specific antigen(PSA) level, PSA rate and ERG were all the risk factors for prostate cancer(P<0.05). According to multivariate regression analysis, PSA rate and ERG were independent risk factors for prostate cancer(P<0.05). All the 59 patients with prostate cancer underwent surgical treatment, where lymph node metastasis was found in 27 cases. The aberration rate threshold of ERG was 2.6% and the area under the ROC curve was 0.820, larger than that of the PSA(0.718), with statistically significant difference(P<0.05). Conclusions The positive expression of ERG can serve as an auxiliary assessment tool of prostate cancer, which is also of predictive value for lymph node metastasis.
引文
[1] 郭琦,余英豪.前列腺癌中TMPRSS2-ERG融合基因和ERG蛋白表达及其意义[J].临床与实验病理学杂志,2014,30(10):1099-1103.
[2] 刘磊,赵调调.腹膜外保留骶前神经对低龄前列腺癌根治术患者勃起功能、精子质量、性生活质量及排尿功能的影响[J].中国性科学,2017,26(9):31-35.
[3] Valerio M,Cerantola Y,Eggener SE,et al.New and established technology in focal ablation of the prostate:A systematic review[J].Eur Urol,2017,71(1):17-34.
[4] 蔡冰,王雷,李华民.P504S/AMACR在穿刺前列腺癌标本中的表达及其临床意义[J].现代肿瘤医学,2018,26(3):423-426.
[5] 董隽,肖立,孙忠全,等.前列腺癌E26转录因子家族基因融合发生率及其与临床病理指标相关性研究[J].中华泌尿外科杂志,2014,35(3):195-199.
[6] 孙文国,夏利,蒋雷鸣,等.TMPRSS2-ERG、AMACR和p63在前列腺癌中的表达及相关性[J].安徽医科大学学报,2012,47(11):1351-1355.
[7] Kiflemariam S,Mignardi M,Ali MA,et al.在前列腺癌中通过原位测序识别TMPRSS2-ERG融合基因转录体、体细胞点突变和基因表达水平[J].魏建国,摘译,许春伟,张博,审校.临床与实验病理学杂志,2015,31(1):9-9.
[8] Park K,Dalton JT,Narayanan R,et al.TMPRSS2:ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia [J].Journal of Clinical Oncology,2014,32(3):206-211.
[9] 巩艳青,张崔建,何世明,等.核转出蛋白对前列腺癌雄激素受体稳定性的调节[J].北京大学学报(医学版),2017,49(4):569-574.
[10] Kolar Z,Burdova A,Jamaspishvili T,et al.Relation of ETS transcription factor family member ERG,androgen receptor and topoisomerase 2β expression to TMPRSS2-ERG fusion status in prostate cancer[J].Neoplasma,2014,61(1):9-16.
[11] 丁奕星,齐隽.TMPRSS2-ETS融合基因在前列腺癌中的研究进展及临床应用前景[J].上海交通大学学报(医学版),2011,31(6):852-857.
[12] 毛易捷,史伟峰,李青,等.TMPRSS2:ERG融合基因与前列腺原位癌和外周转移癌的相关性研究[J].国际检验医学杂志,2013,34(1):44-48.
[13] Tian TV,Tomavo N,Huot L,et al.Identification of novel TMPRSS2:ERG mechanisms in prostate cancer metastasis:Involvement of MMP9 and PLXNA2[J].Oncogene,2014,33(17):2204-2214.
[14] 何亮,李伟,梁建波,等.荧光原位杂交技术检测融合基因对前列腺癌的诊断价值[J].广西医学,2014,12 (2):166-169.
[15] 肖立,朱雄增,WANG Yan,等.TMPRSS2-ERG融合基因在转移性前列腺癌中的表达[J].中华病理学杂志,2011,40(6):392-396.
[16] Robert G,Jannink S,Smit F,et al.Rational basis for the combination of PCA3 and TMPRSS2:ERG gene fusion for prostate cancer diagnosis[J].The Prostate,2013,73(2):113-120.
[17] 斯钦布和,王国强,闫骏,等.前列腺癌患者危险因素分析及不同分级患者术后康复比较[J].疑难病杂志,2015,14(3):269-272.
[18] 贾勇,孙小庆,高健刚,等.青岛市区前列腺癌发病危险因素的病例对照研究[J].中华男科学杂志,2013,19 (8):694-698.
[2] 刘磊,赵调调.腹膜外保留骶前神经对低龄前列腺癌根治术患者勃起功能、精子质量、性生活质量及排尿功能的影响[J].中国性科学,2017,26(9):31-35.
[3] Valerio M,Cerantola Y,Eggener SE,et al.New and established technology in focal ablation of the prostate:A systematic review[J].Eur Urol,2017,71(1):17-34.
[4] 蔡冰,王雷,李华民.P504S/AMACR在穿刺前列腺癌标本中的表达及其临床意义[J].现代肿瘤医学,2018,26(3):423-426.
[5] 董隽,肖立,孙忠全,等.前列腺癌E26转录因子家族基因融合发生率及其与临床病理指标相关性研究[J].中华泌尿外科杂志,2014,35(3):195-199.
[6] 孙文国,夏利,蒋雷鸣,等.TMPRSS2-ERG、AMACR和p63在前列腺癌中的表达及相关性[J].安徽医科大学学报,2012,47(11):1351-1355.
[7] Kiflemariam S,Mignardi M,Ali MA,et al.在前列腺癌中通过原位测序识别TMPRSS2-ERG融合基因转录体、体细胞点突变和基因表达水平[J].魏建国,摘译,许春伟,张博,审校.临床与实验病理学杂志,2015,31(1):9-9.
[8] Park K,Dalton JT,Narayanan R,et al.TMPRSS2:ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia [J].Journal of Clinical Oncology,2014,32(3):206-211.
[9] 巩艳青,张崔建,何世明,等.核转出蛋白对前列腺癌雄激素受体稳定性的调节[J].北京大学学报(医学版),2017,49(4):569-574.
[10] Kolar Z,Burdova A,Jamaspishvili T,et al.Relation of ETS transcription factor family member ERG,androgen receptor and topoisomerase 2β expression to TMPRSS2-ERG fusion status in prostate cancer[J].Neoplasma,2014,61(1):9-16.
[11] 丁奕星,齐隽.TMPRSS2-ETS融合基因在前列腺癌中的研究进展及临床应用前景[J].上海交通大学学报(医学版),2011,31(6):852-857.
[12] 毛易捷,史伟峰,李青,等.TMPRSS2:ERG融合基因与前列腺原位癌和外周转移癌的相关性研究[J].国际检验医学杂志,2013,34(1):44-48.
[13] Tian TV,Tomavo N,Huot L,et al.Identification of novel TMPRSS2:ERG mechanisms in prostate cancer metastasis:Involvement of MMP9 and PLXNA2[J].Oncogene,2014,33(17):2204-2214.
[14] 何亮,李伟,梁建波,等.荧光原位杂交技术检测融合基因对前列腺癌的诊断价值[J].广西医学,2014,12 (2):166-169.
[15] 肖立,朱雄增,WANG Yan,等.TMPRSS2-ERG融合基因在转移性前列腺癌中的表达[J].中华病理学杂志,2011,40(6):392-396.
[16] Robert G,Jannink S,Smit F,et al.Rational basis for the combination of PCA3 and TMPRSS2:ERG gene fusion for prostate cancer diagnosis[J].The Prostate,2013,73(2):113-120.
[17] 斯钦布和,王国强,闫骏,等.前列腺癌患者危险因素分析及不同分级患者术后康复比较[J].疑难病杂志,2015,14(3):269-272.
[18] 贾勇,孙小庆,高健刚,等.青岛市区前列腺癌发病危险因素的病例对照研究[J].中华男科学杂志,2013,19 (8):694-698.