Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers.
Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers.
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DOI：
10.1158/2326-6066.cir-13-0088
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发表时间：
2014-04
影响因子：
10.1
通讯作者：
Zhao Q
中科院分区：
文献类型：
--
作者：
Yao J;Caballero OL;Yung WK;Weinstein JN;Riggins GJ;Strausberg RL;Zhao Q
癌睾丸（CT）抗原是肿瘤免疫治疗的潜在靶点，因为它们在免疫特权生殖细胞和各种恶性肿瘤中表达受限。目前基于CT的免疫治疗的应用主要集中在富含CT表达的肿瘤，如黑色素瘤和肺癌。在这项研究中，我们使用癌症基因组图谱（TCGA）数据集调查了10种常见癌症类型的CT表达。我们发现，CT表达在某些癌症分子亚型中是特异性的和丰富的。例如，HORMAD1、CXorf61、ACTL8和PRAME在乳腺癌基底亚型中高度富集；在肺腺癌的磁样亚型中，MAGE和CSAG最常被激活；PRAME在透明细胞肾细胞癌的ccB亚型中高度上调。CT基因表达和DNA甲基化分析表明，一些CT受表观遗传调控，而其他CT主要受组织和亚型特异性转录因子的控制。我们的研究结果表明，尽管一些ct的表达与患者的预后有关，但并不是很多是独立的预后标志物。因此，具有共享表达模式的ct是异质分子，在不同的癌症和癌症亚型中具有不同的激活模式和功能特性。这些数据提示了CT抗原作为生物标志物和免疫治疗靶点的癌症亚型定向应用。
Cancer-testis (CT) antigens are potential targets for cancer immunotherapy because of their restricted expression in immune-privileged germ cells and various malignancies. Current application of CT-based immunotherapy has been focused on CT expression-rich tumors such as melanoma and lung cancers. In this study, we surveyed CT expression using the Cancer Genome Atlas (TCGA) datasets for ten common cancer types. We show that, CT expression is specific and enriched within certain cancer molecular subtypes. For example, HORMAD1, CXorf61, ACTL8 and PRAME are highly enriched in the basal subtype of breast cancer; MAGE and CSAG are most frequently activated in the magnoid subtype of lung adenocarcinoma; and PRAME is highly upregulated in the ccB subtype of clear cell renal cell carcinoma. Analysis of CT gene expression and DNA methylation indicates that some CTs are regulated epigenetically while others are controlled primarily by tissue- and subtype-specific transcription factors. Our results suggest that although for some CTs expression is associated with patient outcome, not many are independent prognostic markers. Thus, CTs with shared expression pattern are heterogeneous molecules with distinct activation modes and functional properties in different cancers and cancer subtypes. These data suggest a cancer subtype-orientated application of CT antigen as biomarkers and immunotherapeutic targets.