Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma.
Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma.
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DOI：
10.1158/1078-0432.ccr-15-2226
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发表时间：
2016-06-15
期刊：
影响因子：
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通讯作者：
Grimm EA
中科院分区：
文献类型：
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作者：
Ekmekcioglu S;Davies MA;Tanese K;Roszik J;Shin-Sim M;Bassett RL Jr;Milton DR;Woodman SE;Prieto VG;Gershenwald JE;Morton DL;Hoon DS;Grimm EA
使用III期黑色素瘤患者的肿瘤组织的两个独立群组，评价III期黑色素瘤肿瘤中的炎性标志物表达与结果的关联。选择15个感兴趣的标记物进行分析，并通过免疫组织化学测定它们在黑素瘤组织中的表达。在回顾性发现组织微阵列（TMA）（n = 158）中与总生存期（OS）或无复发生存期（RFS）相关的蛋白质随后在独立验证TMA（n = 114）中进行评估。使用考克斯比例风险回归模型评估生存参数和协变量之间的相关性，使用Kaplan-Meier方法估计生存分布，使用对数秩检验比较分布。CD 74在黑色素瘤细胞上的表达是独特的，并且在TMA的发现中，其与有利的患者结局相关（OS：HR，0.53，P = 0.01和RFS：HR，0.56; P = 0.01）。验证数据集证实了CD 74的预后意义，并揭示了MIF和iNOS的缺乏也与生存参数差有关。与蛋白质观察结果一致，在黑色素瘤TCGA数据集中，肿瘤CD 74 mRNA表达也与OS呈正相关（p = 0.003）。我们的数据验证了CD 74作为一个有用的预后肿瘤细胞蛋白标志物与有利的RFS和OS在III期黑色素瘤。MIF在两个TMA中的低表达或阴性表达，以及验证集中的iNOS的低表达或阴性表达也提供了有用的预后数据。对CD 74功能意义的疾病特异性研究是有必要的，其他标志物似乎也很有吸引力。
Inflammatory marker expression in stage III melanoma tumors was evaluated for association with outcome, using two independent cohorts of stage III melanoma patients’ tumor tissues. Fifteen markers of interest were selected for analysis, and their expression in melanoma tissues was determined by immunohistochemistry. Proteins associating with either overall survival (OS) or relapse-free survival (RFS) in the retrospective discovery tissue microarray (TMA) (n = 158) were subsequently evaluated in an independent validation TMA (n = 114). Cox proportional hazards regression models were used to assess the association between survival parameters and covariates, the Kaplan-Meier method to estimate the distribution of survival, and the log-rank test to compare distributions. Expression of CD74 on melanoma cells was unique, and in the discovery TMA it associated with favorable patient outcome (OS: HR, 0.53, P = 0.01 and RFS: HR, 0.56; P = 0.01). The validation dataset confirmed the CD74 prognostic significance and revealed that the absence of MIF and iNOS was also associated with poor survival parameters. Consistent with the protein observation, tumor CD74 mRNA expression also correlated positively (p = 0.003) with OS in the melanoma TCGA dataset. Our data validate CD74 as a useful prognostic tumor cell protein marker associated with favorable RFS and OS in stage III melanoma. Low or negative expression of MIF in both TMAs, and of iNOS in the validation set also provided useful prognostic data. A disease-specific investigation of CD74’s functional significance is warranted, and other markers appear intriguing to pursue.