A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors
A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors
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DOI：
10.1158/1078-0432.ccr-11-2210
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发表时间：
2012-05-01
影响因子：
11.5
通讯作者：
Hengstler，Jan G.
中科院分区：
文献类型：
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作者：
Schmidt，Marcus;Hellwig，Birte;Hengstler，Jan G.
目的：虽然免疫系统在肿瘤预后中的核心作用已被普遍接受，但尚无单一的稳健标志物可用。实验设计：在接收者工作特性分析的基础上，从60个基因的B细胞衍生的后生基因中筛选出稳健的标志物，并分析了1810例乳腺癌、1056例非小细胞肺癌、513例结直肠癌和426例卵巢癌患者的基因表达谱。对330例乳腺癌患者石蜡包埋组织进行蛋白质和RNA水平检测。结果：我们鉴定出免疫球蛋白κC(Ig KC)，它作为单个标志物与整个B细胞元基因具有相似的预测和预后作用。IGKC一直与不同分子亚型的无转移乳腺癌的无转移存活率有关(n=965)，并预测了对基于蒽环类药物的新辅助化疗的反应(n=845；P<；0.001)。此外，IGKC基因表达与非小细胞肺癌和结直肠癌的预后有关。在卵巢癌中没有观察到关联。330例乳腺癌患者石蜡包埋组织中IGKC蛋白表达与生存期显著相关。肿瘤浸润性浆细胞被认为是IGKC表达的来源。结论：我们的研究结果为IGKC作为一种新的人类癌症风险分层的诊断标志物提供了支持，并为利用体液免疫反应进行抗癌治疗提供了概念。它可以在几个独立的队列中得到验证，并在新鲜冷冻的RNA以及来自石蜡组织的RNA中进行类似的良好执行，并通过免疫染色在蛋白质水平上进行。©2012 AACR。
Purpose:Although the central role of the immune system for tumor prognosis is generally accepted, a single robust marker is not yet available.Experimental Design:On the basis of receiver operating characteristic analyses, robust markers were identified from a 60-gene B cell–derived metagene and analyzed in gene expression profiles of 1,810 breast cancer; 1,056 non–small cell lung carcinoma (NSCLC); 513 colorectal; and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin-embedded tissue of 330 breast cancer patients. The cell types were identified with immunohistochemical costaining and confocal fluorescence microscopy.Results:We identified immunoglobulin κ C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis-free survival across different molecular subtypes in node-negative breast cancer (n= 965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n= 845;P< 0.001). In addition, IGKC gene expression was prognostic in NSCLC and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin-embedded tissues of 330 breast cancer patients. Tumor-infiltrating plasma cells were identified as the source of IGKC expression.Conclusion:Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anticancer therapy. It could be validated in several independent cohorts and carried out similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.Clin Cancer Res; 18(9); 2695–703. ©2012 AACR.