CD73 Expression Is an Independent Prognostic Factor in Prostate Cancer
CD73 Expression Is an Independent Prognostic Factor in Prostate Cancer
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DOI：
10.1158/1078-0432.ccr-15-1181
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发表时间：
2016-01-01
影响因子：
11.5
通讯作者：
Stagg, John
中科院分区：
文献类型：
--
作者：
Leclerc, Bruno G.;Charlebois, Roxanne;Stagg, John
目的：CD73是一种腺苷生成外泌酶，可抑制包括前列腺癌在内的小鼠癌症模型的抗肿瘤免疫。尽管在各种类型的癌症中，高水平的CD73与预后不良有关，但CD73在前列腺癌中的临床影响尚不清楚。实验设计：通过组织微阵列（TMA）检测285例前列腺癌患者的CD73蛋白表达和CD8（+）细胞密度，评估其预后价值。正常邻近组织和肿瘤组织重复评估。结果：单因素和多因素分析显示，正常邻近前列腺上皮中高水平的CD73与较短的生化复发（BCR）无生存期显著相关。值得注意的是，CD73在正常上皮中的表达对前列腺浸润性CD8（+）细胞具有阴性预后价值。令人惊讶的是，在单变量分析中，肿瘤基质中高水平的CD73与更长的无bcr生存期相关。体外研究发现腺苷信号通过A2B腺苷受体抑制人前列腺癌细胞NF-kappa B活性。与这些结果一致的是，前列腺肿瘤基质中CD73的表达与前列腺肿瘤细胞核中p65的表达呈负相关。结论：我们的研究表明CD73是前列腺癌的一个独立预后因素。我们的数据支持一个模型，即前列腺上皮中的CD73表达抑制CD8(+) T细胞的免疫监视，而肿瘤基质中的CD73表达通过A2B腺苷受体信号传导降低肿瘤细胞中的nf - κ B信号传导。CD73的表达，包括在正常邻近前列腺上皮中的表达，因此可以有效地区分侵袭性和惰性前列腺癌。AACR (C) 2015。
Purpose: CD73 is an adenosine-generating ecto-enzyme that suppresses antitumor immunity in mouse models of cancer, including prostate cancer. Although high levels of CD73 are associated with poor prognosis in various types of cancer, the clinical impact of CD73 in prostate cancer remains unclear.Experimental Design: We evaluated the prognostic value of CD73 protein expression and CD8(+) cell density in 285 cases of prostate cancer on tissue microarray (TMA). Normal adjacent and tumor tissues were evaluated in duplicates.Results: Univariate and multivariate analyses revealed that high levels of CD73 in normal adjacent prostate epithelium were significantly associated with shorter biochemical recurrence (BCR)-free survival. Notably, CD73 expression in normal epithelium conferred a negative prognostic value to prostate-infiltrating CD8(+) cells. Surprisingly, high levels of CD73 in the tumor stroma were associated with longer BCR-free survival in univariate analysis. In vitro studies revealed that adenosine signaling inhibited NF-kappa B activity in human prostate cancer cells via A2B adenosine receptors. Consistent with these results, CD73 expression in the prostate tumor stroma negatively correlated with p65 expression in the nuclei of prostate tumor cells.Conclusions: Our study revealed that CD73 is an independent prognostic factor in prostate cancer. Our data support a model in which CD73 expression in the prostate epithelium suppresses immunosurveillance by CD8(+) T cells, whereas CD73 expression in the tumor stroma reduces NF-kappa B signaling in tumor cells via A2B adenosine receptor signaling. CD73 expression, including in normal adjacent prostate epithelium, can thus effectively discriminate between aggressive and indolent forms of prostate cancer. (C)2015 AACR.