尿PCA3在前列腺癌中的临床价值
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摘要
目的探讨尿前列腺癌抗原3(PCA3)基因表达水平及与血清前列腺特异性抗原(PSA)的表达水平,及其与肿瘤分化程度的关系。方法选择81例因血清PSA表达升高和(或)直肠指诊异常行前列腺穿刺活检的患者。采用苏木精-伊红(HE)染色及免疫组化鸡尾酒染色明确病理活检结果,定量-实时逆转录聚合酶链反应(qRT-PCR)检测尿PCA3 m RNA表达水平,并分析其与肿瘤分化程度的关系。前列腺癌患者尿PCA3 mRNA和血清PSA表达水平间的相关性采用线性回归分析。结果 81例患者的前列腺活检组织中,诊断前列腺癌阳性53例,阴性28例。前列腺癌患者尿PCA3 mRNA和血清PSA表达水平,均明显高于非前列腺癌患者(P﹤0.01);前列腺癌患者尿PCA3 m RNA表达水平与血清PSA表达水平无线性相关关系(P﹥0.05)。PCA3 mRNA高表达组患者Gleason评分明显高于低表达组患者(P﹤0.01),尿PCA3高表达倾向低、中度分化(P﹤0.01)。尿PCA3 mRNA高表达组患者NME1、NME3和SPARCL1 mRNA表达水平均明显低于低水平组患者(P﹤0.01);SPOCK1和survivin m RNA表达水平均明显高于低表达组患者(P﹤0.01)。结论前列腺癌患者尿PCA3 mRNA及血清PSA表达水平明显升高,但二者间无线性关系。前列腺癌患者尿PCA3 mRNA高表达时,NME1、NME3和SPARCL1mRNA表达水平及分化程度均降低,SPOCK1和survivin mRNA表达水平升高。
Objective To explore the urine prostate cancer antigen 3(PCA3) gene and serum prostate specific antigen(PSA) expression in human prostate cancer and its molecular mechanisms in tumor differentiation. Method A total of 81 samples of prostate cancer tissues were collected by diagnostic prostate puncture from patients with elevated PSA expression and(or) abnormal rectal examination results. The pathological results were determined by hematoxylin and eosin(HE) staining and immunohistochemical cocktail staining, and then quantitative realtime polymerase chain reaction(qRTPCR) was applied to detect urine PCA3 mRNA expression and analyze its association with tumor differentiation. Besides,the correlation between urine PCA3 m RNA and serum PSA expression was evaluated by linear regression analysis. Result Of the 81 patients with prostate biopsy, 53 patients of positive prostate cancer and 28 negative patients were identified.The level of urine PCA3 m RNA and serum PSA expression were significantly higher in prostate cancer patients than in those with negative lesions(P<0.01), meanwhile, there was no linear correlation between urine PCA3 mRNA and serum PSA expression in prostate cancer patients(P>0.05). Higher PCA3 mRNA was associated with higher Gleason score compared with those with lower expression(P<0.01), higher expression of urine PCA3 mRNA tended to be poorly or moderately differentiated(P<0.01). In addition, expression of urine PCA3 mRNA was negatively correlated with NME1, NME3 and SPARCL1 mRNA expression(P<0.01), and positively correlated with PCA3 mRNA, SPOCK1 and survivin mRNA expression(P<0.01). Conclusion The expression of urine PCA3 and serum PSA were higher in prostate cancer patients,though there was no linear correlation observed in between. urine PCA3 expression in prostate cancer was negatively correlated with NME1, NME3, SPARCL1 m RNA expression and the degree of differentiation, while positively correlated with SPOCK1 and survivin mRNA expression.
Objective To explore the urine prostate cancer antigen 3(PCA3) gene and serum prostate specific antigen(PSA) expression in human prostate cancer and its molecular mechanisms in tumor differentiation. Method A total of 81 samples of prostate cancer tissues were collected by diagnostic prostate puncture from patients with elevated PSA expression and(or) abnormal rectal examination results. The pathological results were determined by hematoxylin and eosin(HE) staining and immunohistochemical cocktail staining, and then quantitative realtime polymerase chain reaction(qRTPCR) was applied to detect urine PCA3 mRNA expression and analyze its association with tumor differentiation. Besides,the correlation between urine PCA3 m RNA and serum PSA expression was evaluated by linear regression analysis. Result Of the 81 patients with prostate biopsy, 53 patients of positive prostate cancer and 28 negative patients were identified.The level of urine PCA3 m RNA and serum PSA expression were significantly higher in prostate cancer patients than in those with negative lesions(P<0.01), meanwhile, there was no linear correlation between urine PCA3 mRNA and serum PSA expression in prostate cancer patients(P>0.05). Higher PCA3 mRNA was associated with higher Gleason score compared with those with lower expression(P<0.01), higher expression of urine PCA3 mRNA tended to be poorly or moderately differentiated(P<0.01). In addition, expression of urine PCA3 mRNA was negatively correlated with NME1, NME3 and SPARCL1 mRNA expression(P<0.01), and positively correlated with PCA3 mRNA, SPOCK1 and survivin mRNA expression(P<0.01). Conclusion The expression of urine PCA3 and serum PSA were higher in prostate cancer patients,though there was no linear correlation observed in between. urine PCA3 expression in prostate cancer was negatively correlated with NME1, NME3, SPARCL1 m RNA expression and the degree of differentiation, while positively correlated with SPOCK1 and survivin mRNA expression.
引文
[1]韩苏军,张思维,陈万青,等.中国前列腺癌死亡现状及流行趋势分析[J].中华泌尿外科杂志, 2012, 33(11):836-839.
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[8]王炜,李传刚,刘辉,等.前列腺特异性抗原对前列腺癌诊断价值的探讨[J].中国医科大学学报, 2016, 45(1):61-65.
[9] Bussemakers MJ, van Bokhoven A, Verhaegh GW, et al.DD3:a new prostate-specific gene, highly overexpressed in prostate cancer[J]. Cancer Res, 1999, 59(23):5975-5979.
[10] Ferreira LB, Palumbo A, de Mello KD, et al. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling[J]. BMC Cancer, 2012, 12:507.
[11] Yang Z, Yu L, Wang Z. PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer[J].Chin J Cancer Res, 2016, 28(1):65-71.
[12] Aubin SM, Reid J, Sarno MJ, et al. PCA3 moIecuIar urine test for predicting repeat prostate biopsy outcome in popuIations at risk:validation in the placebo arm of the dutasteride REDUCE triaI[J]. J UroI, 2010, 184(5):1947-1952.
[13] Postel EH. Multiple biochemical activities of NM23/NDP kinase in gene regulation[J]. J Bioenerg Biomembr, 2003,35(1):31-40.
[14]韩玮. SPARCL1基因在肿瘤发生中的作用[J].医学综述, 2016, 22(11):2110-2114.
[15] Kawamata H, Furihata T, Omotehara F, et al. Identification of genes differentially expressed in a newly isolated human metastasizing esophageal cancer cell line, T.TnAT1, by cDNA microarray[J]. Cancer Sci, 2003, 94(8):699-706.
[16] Jain A, McKnight DA, Fisher LW, et al. Small integrinbinding proteins as serum markers for prostate cancer detection[J]. Clin Cancer Res, 2009, 15(16):5199-5207.
[17] Gretzer MB, Partin AW. PSA markers in prostate cancer detection[J]. Urol Clin North Am, 2003, 30(4):677-686.
[18] De Luca S, Passera R, Cattaneo G, et al. High prostate cancer gene 3(PCA3)scores are associated with elevated prostate imaging reporting and data system(PI-RADS)grade and biopsy gleason score, at magnetic resonance imaging/ultrasonography fusion software-based targeted prostate biopsy after a previous negative standard biopsy[J]. BJU Int, 2016, 118(5):723-730.
[19] Bollito E, De Luca S, Cicilano M, et al. Prostate cancer gene 3 urine assay cutoff in diagnosis of prostate cancer:a validation study on an Italian patient population undergoing first and repeat biopsy[J]. Anal Quant Cytol Histol,2012, 34(2):96-104.
[2] Shilstein SSh, Cortesi M, Breskin A, et al. Prostatic Zn determination for prostate cancer diagnosis[J]. Talanta, 2006,70(5):914-921.
[3]洪西,刘利杰,俞建军.前列腺癌诊断标志物研究进展[J].临床泌尿外科杂志, 2018(12):1012-1015.
[4]王进恩,马春清,祝存海.前列腺癌患者前列腺癌基因3的表达[J].中国医药导报, 2012, 9(12):100-101.
[5] Sanda MG, Feng Z, Howard DH, et al. Association between combined TMPRSS2:ERG and PCA3 RNA urinary testing and detection of aggressive prostate cancer[J]. JAMA Oncol, 2017, 3(8):1085-1093.
[6]方毅,王学梅.经直肠超声剪切波弹性成像诊断外周带前列腺癌及与Gleason评分间关系[J].中国超声医学杂志,2018, 34(12):1122-1125.
[7]何乾,张国辉.前列腺肿瘤标志物的研究进展及临床意义[J].癌症进展, 2017, 15(1):7-9; 14.
[8]王炜,李传刚,刘辉,等.前列腺特异性抗原对前列腺癌诊断价值的探讨[J].中国医科大学学报, 2016, 45(1):61-65.
[9] Bussemakers MJ, van Bokhoven A, Verhaegh GW, et al.DD3:a new prostate-specific gene, highly overexpressed in prostate cancer[J]. Cancer Res, 1999, 59(23):5975-5979.
[10] Ferreira LB, Palumbo A, de Mello KD, et al. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling[J]. BMC Cancer, 2012, 12:507.
[11] Yang Z, Yu L, Wang Z. PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer[J].Chin J Cancer Res, 2016, 28(1):65-71.
[12] Aubin SM, Reid J, Sarno MJ, et al. PCA3 moIecuIar urine test for predicting repeat prostate biopsy outcome in popuIations at risk:validation in the placebo arm of the dutasteride REDUCE triaI[J]. J UroI, 2010, 184(5):1947-1952.
[13] Postel EH. Multiple biochemical activities of NM23/NDP kinase in gene regulation[J]. J Bioenerg Biomembr, 2003,35(1):31-40.
[14]韩玮. SPARCL1基因在肿瘤发生中的作用[J].医学综述, 2016, 22(11):2110-2114.
[15] Kawamata H, Furihata T, Omotehara F, et al. Identification of genes differentially expressed in a newly isolated human metastasizing esophageal cancer cell line, T.TnAT1, by cDNA microarray[J]. Cancer Sci, 2003, 94(8):699-706.
[16] Jain A, McKnight DA, Fisher LW, et al. Small integrinbinding proteins as serum markers for prostate cancer detection[J]. Clin Cancer Res, 2009, 15(16):5199-5207.
[17] Gretzer MB, Partin AW. PSA markers in prostate cancer detection[J]. Urol Clin North Am, 2003, 30(4):677-686.
[18] De Luca S, Passera R, Cattaneo G, et al. High prostate cancer gene 3(PCA3)scores are associated with elevated prostate imaging reporting and data system(PI-RADS)grade and biopsy gleason score, at magnetic resonance imaging/ultrasonography fusion software-based targeted prostate biopsy after a previous negative standard biopsy[J]. BJU Int, 2016, 118(5):723-730.
[19] Bollito E, De Luca S, Cicilano M, et al. Prostate cancer gene 3 urine assay cutoff in diagnosis of prostate cancer:a validation study on an Italian patient population undergoing first and repeat biopsy[J]. Anal Quant Cytol Histol,2012, 34(2):96-104.