Identifying Reproducible Molecular Biomarkers for Gastric Cancer Metastasis with the Aid of Recurrence Information.
Identifying Reproducible Molecular Biomarkers for Gastric Cancer Metastasis with the Aid of Recurrence Information.
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借助复发信息识别胃癌转移的可重复分子生物标志物
DOI：
10.1038/srep24869
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发表时间：
2016-04-25
影响因子：
4.6
通讯作者：
Guo Z
中科院分区：
文献类型：
--
作者：
Li M;Hong G;Cheng J;Li J;Cai H;Li X;Guan Q;Tong M;Li H;Guo Z
准确诊断转移状态对于指导胃癌患者的个体化治疗具有重要意义。然而，常规的肿瘤转移的放射学和病理学检测有相当高的假阴性率，这可能会阻碍胃癌转移相关分子标志物的识别。在本研究中，使用三个数据集，我们首先指出，当转移和非转移组织样本仅用TNM分期来定义时，转移组织和非转移组织样本之间的差异表达基因(Deg)很难在适当的统计对照下被重复检测。然后，假设无法检测到的微转移是早期根治性切除患者复发的主要原因，当患者在肿瘤切除后的随访中出现肿瘤复发时，我们将所有“非转移”样本重新归类为转移样本。通过这种方法，我们能够在重新分类的转移组织和非转移组织之间找到明显和可重复性的DEG，以及区分胃癌转移组织和非转移组织的一致显著的DNA甲基化改变。我们的分析表明，在肿瘤转移的研究中应使用患者的随访复发信息，以减少虚假的无转移标本与未发现的微转移的混杂效应。
To precisely diagnose metastasis state is important for tailoring treatments for gastric cancer patients. However, the routinely employed radiological and pathologic tests for tumour metastasis have considerable high false negative rates, which may retard the identification of reproducible metastasis-related molecular biomarkers for gastric cancer. In this research, using three datasets, we firstly shwed that differentially expressed genes (DEGs) between metastatic tissue samples and non-metastatic tissue samples could hardly be reproducibly detected with a proper statistical control when the metastatic and non-metastatic samples were defined by TNM stage alone. Then, assuming that undetectable micrometastases are the prime cause for recurrence of early stage patients with curative resection, we reclassified all the “non-metastatic” samples as metastatic samples whenever the patients experienced tumour recurrence during follow-up after tumour resection. In this way, we were able to find distinct and reproducible DEGs between the reclassified metastatic and non-metastatic tissue samples and concordantly significant DNA methylation alterations distinguishing metastatic tissues and non-metastatic tissues of gastric cancer. Our analyses suggested that the follow-up recurrence information for patients should be employed in the research of tumour metastasis in order to decrease the confounding effects of false non-metastatic samples with undetected micrometastases.