The Gasdermin E Gene Has Potential as a Pan-Cancer Biomarker, While Discriminating between Different Tumor Types
The Gasdermin E Gene Has Potential as a Pan-Cancer Biomarker, While Discriminating between Different Tumor Types
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DOI：
10.3390/cancers11111810
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发表时间：
2019-11-01
期刊：
影响因子：
5.2
通讯作者：
Van Camp, Guy
中科院分区：
文献类型：
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作者：
Ibrahim, Joe;Op de Beeck, Ken;Van Camp, Guy
由于癌症的发病率和死亡率较高，早期准确的检测对于实现最佳治疗至关重要。分子生物标志物仍然是重要的筛查和检测工具，特别是考虑到新型血液检测。癌症中的 DNA 甲基化与肿瘤发生有关，但其作为生物标志物的价值尚未得到充分探索。在这项研究中，我们使用癌症基因组图谱 (TCGA) 甲基化数据 (N = 6502) 研究了 14 种不同肿瘤类型中 Gasdermin E 基因的甲基化模式。我们能够识别出 6 个 CpG 位点，可以在泛癌环境中有效区分肿瘤和正常样本（AUC = 0.86）。这种泛癌生物标志物的组合在六个独立数据集中得到了验证（AUC = 0.84-0.97）。此外，我们测试了六种 CpG 探针的 74,613 种不同组合，其中我们鉴定了可以区分一种肿瘤类型与所有其他肿瘤类型的肿瘤特异性特征（AUC = 0.79-0.98）。总而言之，甲基化模式在癌症和正常组织之间表现出很大的差异，但也是肿瘤特异性的。我们的分析强调，Gasdermin E 甲基化生物标志物测定不仅具有成为甲基化特异性泛癌检测标志物的潜力，而且还具有区分不同类型肿瘤的能力。
Due to the elevated rates of incidence and mortality of cancer, early and accurate detection is crucial for achieving optimal treatment. Molecular biomarkers remain important screening and detection tools, especially in light of novel blood-based assays. DNA methylation in cancer has been linked to tumorigenesis, but its value as a biomarker has not been fully explored. In this study, we have investigated the methylation patterns of the Gasdermin E gene across 14 different tumor types using The Cancer Genome Atlas (TCGA) methylation data (N = 6502). We were able to identify six CpG sites that could effectively distinguish tumors from normal samples in a pan-cancer setting (AUC = 0.86). This combination of pan-cancer biomarkers was validated in six independent datasets (AUC = 0.84-0.97). Moreover, we tested 74,613 different combinations of six CpG probes, where we identified tumor-specific signatures that could differentiate one tumor type versus all the others (AUC = 0.79-0.98). In all, methylation patterns exhibited great variation between cancer and normal tissues, but were also tumor specific. Our analyses highlight that a Gasdermin E methylation biomarker assay, not only has the potential for being a methylation-specific pan-cancer detection marker, but it also possesses the capacity to discriminate between different types of tumors.