微管相关蛋白1A在前列腺癌中的表达与其临床特征的关系
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摘要
目的探讨微管相关蛋白1A(microtubule associated protein 1A,MAP1A)在前列腺癌中的表达与其临床特征的关系。方法通过免疫组织化学(immunohistochemistry,IHC)染色检测人前列腺癌组织和非癌前列腺组织中MAP1A蛋白质的表达水平,应用实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction,RT-qPCR)检测MAP1A基因在前列腺癌与正常前列腺组织中mRNA的表达差异,进一步使用癌症基因信息数据库(the Cancer Genome Atlas,TCGA)统计分析MAP1A基因表达水平与前列腺癌患者的临床病理学特征之间的关联。结果免疫组化染色结果分析显示,与癌旁正常组织相比,前列腺癌组织中MAP1A的蛋白表达显著降低[免疫组化染色评分(immunoreactive score,IRS):前列腺癌组织为4. 08±1. 58,癌旁正常组织为4. 91±1. 46(P <0. 001)]。MAP1A在前列腺癌及癌旁正常组织中的阳性表达率分别为58. 6%和82. 7%,两者差异具有统计学意义(χ~2=12. 225,P=0. 001)。使用RT-qPCR检测MAP1A mRNA表达,发现其在前列腺癌中表达显著低于正常前列腺组织(P=0. 019)。通过对TCGA数据库进行分析,笔者发现MAP1A在不同临床特征的肿瘤组织中的表达差异具有统计学意义,如患者Gleason评分(P <0. 001),临床病理分期(P=0. 009),是否转移(P=0. 008),总体生存率(P=0. 049)。结论 MAP1A在前列腺癌中表达下调且与肿瘤组织的分期有关,分期越晚,MAP1A的表达越低,这提示其可能参与了前列腺癌的发生、发展。
Objective To investigate the expression of MAP1A in prostate cancer and its relationship with clinical features. Methods The expression of MAP1A at the protein level in human prostate cancer and non-cancerous prostate tissue was detected with immunohistochemistry,and it was further validated with quantitative real-time polymerase chain reaction( RT-qPCR) at the mRNA level.Subsequently,the association of MAP1A expression with the clinical characteristics of the patients with prostate cancer was statistically analyzed with the Cancer Genome Atlas( TCGA) database. Results Immunohistochemistry stains showed that the protein expression of MAP1A was significantly decreased in prostate cancer tissues compared with adjacent normal tissues[immunoreactive score( IRS) :Prostate cancer tissue = 4. 08 ± 1. 58,Tumor-adjacent normal tissue = 4. 91 ± 1. 46,P < 0. 001]. The positive expression rates of MAP1A in PCa tissue samples and adjacent normal tissue samples were 58. 6% and 82. 7%,respectively,indicating a statistically significant difference( χ~2= 12. 225,P = 0. 001). MAP1A mRNA expression was detected with quantitative real-time PCR and it was significantly lower in prostate cancer than in normal prostate tissue( P = 0. 019). Analysis of TCGA data suggested,that the expression of MAP1A is significantly different in the tumor tissues with different clinical characteristics,such as Gleason score( P < 0. 001),clinical pathological stage( P = 0. 009),metastasis( P = 0. 008),and overall survival rate( P = 0. 049). Conclusion MAP1A is down-regulated in prostate cancer and is associated with the staging of tumor tissue. The later stage of tumor tissue,the lower the expression of MAP1A,suggesting that MAP1A is related to the development and progression of prostate cancer.
Objective To investigate the expression of MAP1A in prostate cancer and its relationship with clinical features. Methods The expression of MAP1A at the protein level in human prostate cancer and non-cancerous prostate tissue was detected with immunohistochemistry,and it was further validated with quantitative real-time polymerase chain reaction( RT-qPCR) at the mRNA level.Subsequently,the association of MAP1A expression with the clinical characteristics of the patients with prostate cancer was statistically analyzed with the Cancer Genome Atlas( TCGA) database. Results Immunohistochemistry stains showed that the protein expression of MAP1A was significantly decreased in prostate cancer tissues compared with adjacent normal tissues[immunoreactive score( IRS) :Prostate cancer tissue = 4. 08 ± 1. 58,Tumor-adjacent normal tissue = 4. 91 ± 1. 46,P < 0. 001]. The positive expression rates of MAP1A in PCa tissue samples and adjacent normal tissue samples were 58. 6% and 82. 7%,respectively,indicating a statistically significant difference( χ~2= 12. 225,P = 0. 001). MAP1A mRNA expression was detected with quantitative real-time PCR and it was significantly lower in prostate cancer than in normal prostate tissue( P = 0. 019). Analysis of TCGA data suggested,that the expression of MAP1A is significantly different in the tumor tissues with different clinical characteristics,such as Gleason score( P < 0. 001),clinical pathological stage( P = 0. 009),metastasis( P = 0. 008),and overall survival rate( P = 0. 049). Conclusion MAP1A is down-regulated in prostate cancer and is associated with the staging of tumor tissue. The later stage of tumor tissue,the lower the expression of MAP1A,suggesting that MAP1A is related to the development and progression of prostate cancer.
引文
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[20] Helgstrand J T,Roder M A,Klemann N,et al. Diagnostic characteristics of lethal prostate cancer[J]. Eur J Cancer,2017,84:18-26.
[21] Li S,Ma Y,Xie C,et al. Eph A6 promotes angiogenesis and prostate cancer metastasis and is associated w ith human prostate cancer progression[J]. Oncotarget,2015,6(26):22587-22597.
[22] Kendel F,Helbig L,Neumann K,et al. Patients'perceptions of mortality risk for localized prostate cancer vary markedly depending on their treatment strategy[J]. Int J Cancer.,2016,139(4):749-753.
[23]冯思坛,施鑫.微管相关蛋白与肿瘤关系的研究进展[N].医学研究生学报,2013,26(8):878-881.
[24] Fink J K,Jones S M,Esposito C,et al. Human microtubule-associated protein 1a(M AP1A)gene:genomic organization,c DNA sequence,and developmental-and tissue-specific expression[J]. Genomics,1996,35(3):577-585.
[25] Liu Y,Lee J W,Ackerman S L,et al. Mutations in the microtubule-associated protein 1A(M ap1a)gene cause Purkinje cell degeneration[J]. J Neurosci,2015,35(11):4587-4598.
[26] Meyer M A. Highly expressed genes in human high grade gliomas:immunohistochemical analysis of data from the human protein atlas[J]. Neurol Int,2014,6(2):5348.
[27] Knutson T P,Daniel A R,Fan D,et al. Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression[J]. Breast Cancer Res,2012,14(3):R95.
[28] Jiang X,Zhong W,Huang H,et al. Autophagy defects suggested by low levels of autophagy activator M AP1S and high levels of autophagy inhibitor LRPPRC predict poor prognosis of prostate cancer patients[J]. M ol Carcinog,2015,54(10):1194-1204.
[2] Siegel R L,Miller K D,Jemal A. Cancer statistics,2018[J]. CA Cancer J Clin,2018,68(1):7-30.
[3] Bray F,Ferlay J,Soerjomataram I,et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality w orldw ide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
[4] Chen W,Zheng R,Baade P D,et al. Cancer statistics in China,2015[J]. CA Cancer J Clin,2016,66(2):115-132.
[5] Gerhauser C,Favero F,Risch T,et al. Molecular evolution of early-onset prostate cancer identifies molecular risk markers and clinical trajectories[J]. Cancer Cell,2018,34(6):996-1011.
[6] Wedge D C,Gundem G,Mitchell T,et al. Sequencing of prostate cancers identifies new cancer genes,routes of progression and drug targets[J]. Nat Genet,2018,50(5):682-692.
[7] Cucchiara V,Cooperberg M R,Dall'Era M,et al. Genomic markers in prostate cancer decision making[J]. Eur Urol,2018,73(4):572-582.
[8] Halpain S,Dehmelt L. The MAP1 family ofmicrotubuleassociated proteins[J]. Genome Biol,2006,7(6):224.
[9] Chu J,Li N,Gai W. Identification of genes that predict the biochemical recurrence of prostate cancer[J]. Oncol Lett,2018,16(3):3347-3452.
[10] Canes D. Prostate cancer:Determining optimal therapy of early-stage disease remainscomplicated[J]. Nat Rev Urol,2016,13(12):703-704.
[11] Mc Phail S,Johnson S,Greenberg D,et al. Stage at diagnosis and early mortality from cancer in England[J]. Br J Cancer,2015,112:S108-S115.
[12]马悦,陈弋生.前列腺癌精准诊断的新进展[J].中华男科学杂志,2016,22(11):1030-1033.
[13]张振奇,刘桂丽,夏小彬,等.血清PHI和尿PCA3联合检测评分对PSA灰区前列腺癌诊断价值探讨[J].中华肿瘤防治杂志,2018,25(5):329-333.
[14]赖亚明,韩斌,吴斌. Gleason评分对前列腺癌转归预测意义[J].中华肿瘤防治杂志,2018,25(13):951-955.
[15] Thompson I M,Pauler D K,Goodman P J,et al. Prevalence of prostate cancer among men w ith a prostate specific antigen level
[16] Mistry K,cable G. Meta-analysis of prostate-specific antigen and digital rectal examination as screening tests for prostate carcinoma[J]. J Am Board Fam Pract,2003,16(2):95-101.
[17]年新文,任善成,许传亮.前列腺癌早期诊断标志物的研究进展[J].临床泌尿外科杂志,2016,31(9):852-855.
[18] Kazzazi A,Momtahen S,Bruhn A,et al. New findinfs in localized and advanced prostate cancer:AUA 2011 review[J]. Can J Urol,2011,18(3):5683-5688.
[19] Litwin M S,Tan H J. The diagnosis and treatment of prostate cancer:a review[J]. JAM A,2017,317(24):2532-2542.
[20] Helgstrand J T,Roder M A,Klemann N,et al. Diagnostic characteristics of lethal prostate cancer[J]. Eur J Cancer,2017,84:18-26.
[21] Li S,Ma Y,Xie C,et al. Eph A6 promotes angiogenesis and prostate cancer metastasis and is associated w ith human prostate cancer progression[J]. Oncotarget,2015,6(26):22587-22597.
[22] Kendel F,Helbig L,Neumann K,et al. Patients'perceptions of mortality risk for localized prostate cancer vary markedly depending on their treatment strategy[J]. Int J Cancer.,2016,139(4):749-753.
[23]冯思坛,施鑫.微管相关蛋白与肿瘤关系的研究进展[N].医学研究生学报,2013,26(8):878-881.
[24] Fink J K,Jones S M,Esposito C,et al. Human microtubule-associated protein 1a(M AP1A)gene:genomic organization,c DNA sequence,and developmental-and tissue-specific expression[J]. Genomics,1996,35(3):577-585.
[25] Liu Y,Lee J W,Ackerman S L,et al. Mutations in the microtubule-associated protein 1A(M ap1a)gene cause Purkinje cell degeneration[J]. J Neurosci,2015,35(11):4587-4598.
[26] Meyer M A. Highly expressed genes in human high grade gliomas:immunohistochemical analysis of data from the human protein atlas[J]. Neurol Int,2014,6(2):5348.
[27] Knutson T P,Daniel A R,Fan D,et al. Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression[J]. Breast Cancer Res,2012,14(3):R95.
[28] Jiang X,Zhong W,Huang H,et al. Autophagy defects suggested by low levels of autophagy activator M AP1S and high levels of autophagy inhibitor LRPPRC predict poor prognosis of prostate cancer patients[J]. M ol Carcinog,2015,54(10):1194-1204.