前列腺癌组织B7-H4蛋白表达水平及其与患者不良预后的关系
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摘要
目的:探讨B7-H4在前列腺癌组织中的表达及其预后意义。方法:采用免疫组织化学染色检测72例前列腺癌和50例良性前列腺增生组织B7-H4蛋白表达水平,Kaplan-Meier检验计算B7-H4表达与前列腺癌总体生存率的关系,Cox比例风险模型分析影响患者预后的因素。结果:前列腺癌组织B7-H4高表达率为83.3%(60/72),前列腺增生组织为32.0%(16/50),前列腺癌组织B7-H4高表达率明显高于前列腺增生组织(χ~2=33.105,P<0.001)。B7-H4在Gleason评分8～10分中的阳性表达率明显高于2～7分组,Ⅲ—Ⅳ组B7-H4阳性表达率明显高于Ⅰ—Ⅱ组,淋巴结转移组B7-H4阳性表达率明显高于无淋巴结转移组(P<0.05)。Gleason评分越高,中位生存期越短;Ⅲ—Ⅳ期中位生存期明显低于Ⅰ—Ⅱ期,淋巴结转移的患者中位生存期更短,B7-H4高表达越高中位生存期明显低于B7-H4低表达(均P<0.05);Gleason评分、TNM分期、淋巴结转移、B7-H4蛋白是影响前列腺癌患者预后的独立危险因素(均P<0.05)。结论:前列腺癌组织中B7-H4呈高表达,可以作为前列腺癌预后评估的分子标志物之一。
Objective: To explore the expression of B7-H4 in prostate cancer tissue and its value as a prognostic biomarker for poor survival. Methods: The protein expression of B7-H4 was measured by immunohistochemistry assay in 72 prostate cancer tissues and 50 benign prostatic hyperplasia tissues, the relationship between B7-H4 expression and over-all survival in prostate cancer patients was identified by Kaplan-Meier, the prognostic factors of patients were calculated by Cox proportional hazard regression model. Results: The high expression rate of B7-H4 in the prostate cancer group was 83.3%(60/72), while 32.0%(16/50) in the prostatic hyperplasia group, the high expression rate of B7-H4 in the prostate cancer group was significantly lower than that in the prostatic hyperplasia group, the difference was statistically significant(χ~2=33.105, P<0.001). The high expression rate of B7-H4 in the 8-10 score group was markedly than that in the 2-7 score group, it was higher in Ⅲ-Ⅳ group than in the Ⅰ-Ⅱ group, also it was obviously higher in lymph node metastasis group was obviously higher than in the non-lymph node metastasis group, the difference was statistically significant(P<0.05). The median survival in the prostate cancer patients was negatively correlated with the Gleason score, TNM stage, lymph node metastasis and B7-H4 expression(all P<0.05). Besides, Gleason score, TNM stage, lymph node metastasis and B7-H4 were independent risk factors for the poor prognostic of prostate cancer(all P<0.05). Conclusion: The expression of B7-H4 is up-regulated in the prostate cancer, and its can be used as a biomarker for prognostic of prostate cancer patients.
Objective: To explore the expression of B7-H4 in prostate cancer tissue and its value as a prognostic biomarker for poor survival. Methods: The protein expression of B7-H4 was measured by immunohistochemistry assay in 72 prostate cancer tissues and 50 benign prostatic hyperplasia tissues, the relationship between B7-H4 expression and over-all survival in prostate cancer patients was identified by Kaplan-Meier, the prognostic factors of patients were calculated by Cox proportional hazard regression model. Results: The high expression rate of B7-H4 in the prostate cancer group was 83.3%(60/72), while 32.0%(16/50) in the prostatic hyperplasia group, the high expression rate of B7-H4 in the prostate cancer group was significantly lower than that in the prostatic hyperplasia group, the difference was statistically significant(χ~2=33.105, P<0.001). The high expression rate of B7-H4 in the 8-10 score group was markedly than that in the 2-7 score group, it was higher in Ⅲ-Ⅳ group than in the Ⅰ-Ⅱ group, also it was obviously higher in lymph node metastasis group was obviously higher than in the non-lymph node metastasis group, the difference was statistically significant(P<0.05). The median survival in the prostate cancer patients was negatively correlated with the Gleason score, TNM stage, lymph node metastasis and B7-H4 expression(all P<0.05). Besides, Gleason score, TNM stage, lymph node metastasis and B7-H4 were independent risk factors for the poor prognostic of prostate cancer(all P<0.05). Conclusion: The expression of B7-H4 is up-regulated in the prostate cancer, and its can be used as a biomarker for prognostic of prostate cancer patients.
引文
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[10] 王利飞,崔澂,刘翠莲等.协同共刺激分子B7- H4参与肿瘤免疫逃逸的研究进展[J].中国免疫学杂志,2015,(1):139- 141.
[11] THOMPSON R H,KWON E D,ALLISON J P. Inhibitors of B7- CD28 costimulation in urologic malignancies[J]. Immunotherapy,2009,1(1):129- 139.
[12] 梁克,谢锐,张万青,等.B7- H4和细胞分裂周期蛋白42在非小细胞肺癌组织中的表达及其临床意义[J].中华实验外科杂志,2016,33(8):1903- 1905.
[13] DANGAJ D,LANITIS E,ZHAO A, et al.Novel recombinant human B7- H4 antibodies overcome tumoral immune escape to potentiate T- cell antitumor responses[J]. Cancer Res, 2013,73(15):4820- 4829.
[14] CHEN C,QU QX,SHEN Y, et al.Induced expression of B7- H4 on the surface of lung cancer cell by the tumor- associated macrophages: A potential mechanism of immune escape[J]. Cancer Lett,2012,317(1):99- 105.
[15] 苏欢,陈明.炎症反应与肿瘤微环境对前列腺癌作用机制的研究进展[J].东南大学学报:医学版,2017,36(5):847- 851.
[16] DARMOCHWAL- KOLARZ D,SERAFIN A,TABARKIEWICZ J, et al.The expressions of co- stimulatory molecules are altered on putative antigen- presenting cells in cord blood[J]. Am J Reprod Immunol,2013,69(2):180- 187.
[17] XU Y,ZHU S,SONG M, et al.B7- H4 expression and its role in interleukin- 2/interferon treatment of clear cell renal cell carcinoma[J]. Oncol Lett,2014,7(5):1474- 1478.
[18] 滕月,何彩云,左小航,等.B7- H4在子宫内膜癌组织中的表达及其临床意义[J].医学临床研究,2009,26(9):1606- 1608.
[2] VERMASSEN T,VAN PRAET C,VANDERSCHAEGHE D, et al.Capillary electrophoresis of urinary prostate glycoproteins assists in the diagnosis of prostate cancer[J]. Electrophoresis,2014,35(7):1017- 1024.
[3] 韩苏军,张思维,陈万青,等.中国前列腺癌发病现状和流行趋势分析[J].临床肿瘤学杂志,2013,18(4):330- 334.
[4] DARMOCHWAL- KOLARZ D,KLUDKA- STERNIK M,KOLARZ B, et al.The expression of B7- H1 and B7- H4 co- stimulatory molecules on myeloid and plasmacytoid dendritic cells in pre- eclampsia and normal pregnancy[J]. J Reprod Immunol,2013,99(1- 2):33- 38.
[5] ZHANG L,WU H,LU D, et al.The costimulatory molecule B7- H4 promote tumor progression and cell proliferation through translocating into nucleus[J]. Oncogene,2013, 32(46): 5347- 5358.
[6] 鲁常青,李青,王辉,等.协同刺激分子B7- H1、B7- H4和叉状头/翅膀状螺旋转录因子阳性调节性T细胞在胃癌中的表达及其临床意义[J].中华实验外科杂志,2014,31(3):492- 494.
[7] LIANG M,LI J,WANG D, et al.T- cell infiltration and expressions of T lymphocyte co- inhibitory B7- H1 and B7- H4 molecules among colorectal cancer patients in northeast China's Heilongjiang province[J]. Tumour Biol,2014,35(1):55- 60.
[8] QIAN Y,HONG B,SHEN L, et al.B7- H4 enhances oncogenicity and inhibits apoptosis in pancreatic cancer cells[J].Cell Tissue Res,2013,353(1):139- 151.
[9] 黄卫,陈湘.可溶性B7- H4在膀胱癌诊断中的价值[J].中国现代医学杂志,2015,25(30):65- 67.
[10] 王利飞,崔澂,刘翠莲等.协同共刺激分子B7- H4参与肿瘤免疫逃逸的研究进展[J].中国免疫学杂志,2015,(1):139- 141.
[11] THOMPSON R H,KWON E D,ALLISON J P. Inhibitors of B7- CD28 costimulation in urologic malignancies[J]. Immunotherapy,2009,1(1):129- 139.
[12] 梁克,谢锐,张万青,等.B7- H4和细胞分裂周期蛋白42在非小细胞肺癌组织中的表达及其临床意义[J].中华实验外科杂志,2016,33(8):1903- 1905.
[13] DANGAJ D,LANITIS E,ZHAO A, et al.Novel recombinant human B7- H4 antibodies overcome tumoral immune escape to potentiate T- cell antitumor responses[J]. Cancer Res, 2013,73(15):4820- 4829.
[14] CHEN C,QU QX,SHEN Y, et al.Induced expression of B7- H4 on the surface of lung cancer cell by the tumor- associated macrophages: A potential mechanism of immune escape[J]. Cancer Lett,2012,317(1):99- 105.
[15] 苏欢,陈明.炎症反应与肿瘤微环境对前列腺癌作用机制的研究进展[J].东南大学学报:医学版,2017,36(5):847- 851.
[16] DARMOCHWAL- KOLARZ D,SERAFIN A,TABARKIEWICZ J, et al.The expressions of co- stimulatory molecules are altered on putative antigen- presenting cells in cord blood[J]. Am J Reprod Immunol,2013,69(2):180- 187.
[17] XU Y,ZHU S,SONG M, et al.B7- H4 expression and its role in interleukin- 2/interferon treatment of clear cell renal cell carcinoma[J]. Oncol Lett,2014,7(5):1474- 1478.
[18] 滕月,何彩云,左小航,等.B7- H4在子宫内膜癌组织中的表达及其临床意义[J].医学临床研究,2009,26(9):1606- 1608.
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