Prognostic impact of CD73 and A2A adenosine receptor expression in non-small-cell lung cancer.
Prognostic impact of CD73 and A2A adenosine receptor expression in non-small-cell lung cancer.
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DOI：
10.18632/oncotarget.14434
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发表时间：
2017-01-31
期刊：
影响因子：
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通讯作者：
Sugimura H
中科院分区：
文献类型：
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作者：
Inoue Y;Yoshimura K;Kurabe N;Kahyo T;Kawase A;Tanahashi M;Ogawa H;Inui N;Funai K;Shinmura K;Niwa H;Suda T;Sugimura H
在免疫细胞中，CD73将细胞外AMP脱磷酸化并转化为腺苷，腺苷结合A2A腺苷受体（A2AR）。阻断这种相互作用，在肿瘤微环境中诱导免疫抑制的小生境，代表了一种潜在的新治疗策略。然而，CD73和A2AR在非小细胞肺癌（NSCLC）中表达的临床意义尚未得到彻底研究。在这里，我们评估了CD73和A2AR蛋白表达水平，免疫组化组织芯片包含642个切除的NSCLC标本。此外，我们比较了133对原发肿瘤和淋巴结转移的表达谱。CD73和A2AR表达水平在女性中显著高于男性，从不吸烟者中显著高于曾经吸烟者，腺癌中显著高于鳞状细胞癌。在腺癌中，TTF-1阳性和突变型EGFR阳性肿瘤中的CD73和A2AR表达显著高于其对应物。与CD73相比，A2AR在原发灶和淋巴结转移灶中的表达更不一致。在NSCLC患者中，在多变量考克斯回归分析中，CD73高表达是总生存期[风险比（HR），2.18; 95%置信区间（CI），1.38 - 3.46]和无复发生存期（HR，2.05; 95% CI，1.42 - 2.95）预后不良的独立指标。相反，A2 AR高表达是总生存期（HR，0.70; 95% CI，0.50 - 0.98）和无复发生存期（HR，0.74; 95% CI，0.56 - 0.97）的良好预后的独立预测因子。总之，这些发现表明，CD73和A2AR具有相反的预后作用，尽管涉及CD73或A2AR表达的病例具有一些共同的临床病理学特征。
In immune cells, CD73 dephosphorylates and converts extracellular AMP into adenosine, which binds the A2A adenosine receptor (A2AR). Blockade of this interaction, which induces an immunosuppressed niche in the tumor microenvironment, represents a potential novel treatment strategy. The clinical significance of CD73 and A2AR expression in non-small-cell lung cancer (NSCLC), however, has yet to be thoroughly investigated. Here we evaluated CD73 and A2AR protein expression levels using immunohistochemistry in tissue microarrays containing 642 resected NSCLC specimens. Furthermore, we compared the expression profiles of 133 paired primary tumors and lymph node metastases. CD73 and A2AR expression levels were significantly higher in females than in males, in never smokers than in ever smokers, and in adenocarcinomas than in squamous cell carcinomas. Among adenocarcinomas, significantly higher CD73 and A2AR expression was observed in TTF-1-positive and mutant EGFR-positive tumors than in their counterparts. Compared with CD73, A2AR expression was more inconsistent between primary tumors and lymph node metastases. Among NSCLC patients, high CD73 expression was an independent indicator of poor prognosis in multivariate Cox regression analyses for overall survival [hazard ratio (HR), 2.18; 95% confidence interval (CI), 1.38–3.46] and recurrence-free survival (HR, 2.05; 95% CI, 1.42–2.95). In contrast, high A2AR expression was an independent predictor of favorable prognosis for overall survival (HR, 0.70; 95% CI, 0.50–0.98) and recurrence-free survival (HR, 0.74; 95% CI, 0.56–0.97). Together, these findings indicate that CD73 and A2AR have opposing prognostic effects, although cases involving CD73 or A2AR expression share some clinicopathological features.