Department of Urinary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150006, Heilongjiang, People's Republic of China.
J Transl Med. 2019 May 27;17(1):177. doi: 10.1186/s12967-019-1927-y.
Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cancer in adults, and it is responsible for approximately 90-95% of cases. Although extensive evidence has suggested that many immune- and inflammation-related genes could serve as effective biomarkers in KIRC, the potential associations among immune-, inflammation- and KIRC-related genes has not been sufficiently understood.
Here, we integrated multiple levels of data to construct an immune-, inflammation- or KIRC-directed neighbour network (IIKDN network) and a KIRC-related gene-directed network (KIRCD network).
Our analysis suggested that immune- and inflammation-related genes in the network have special topological characteristics and expression patterns related to KIRC. We further identified five core clusters that showed a tighter network structure and stronger correlation of expression from the KIRCD network. Specifically, multiple-level molecular characteristics were systematically portrayed, including somatic mutation, copy-number variant and DNA methylation for the genes in five core clusters. We discovered that the genes showed strong correlation with respect to the expression and methylation levels in these five core clusters. These five core clusters could become special prognostic biomarkers for KIRC, and functional analysis showed that they were associated with activation of the immune and inflammation systems and cancer progression.
Our findings highlighted the novel role of the immune and inflammation genes in KIRC.
肾透明细胞癌（KIRC）是成人中最常见的肾癌类型，约占 90-95%的病例。尽管有大量证据表明，许多免疫和炎症相关基因可以作为 KIRC 的有效生物标志物，但免疫、炎症和 KIRC 相关基因之间的潜在关联尚未得到充分理解。
在这里，我们整合了多个层次的数据来构建一个免疫、炎症或 KIRC 导向的邻居网络（IIKDN 网络）和一个 KIRC 相关基因导向的网络（KIRCD 网络）。
我们的分析表明，网络中的免疫和炎症相关基因具有与 KIRC 相关的特殊拓扑特征和表达模式。我们进一步从 KIRCD 网络中鉴定出五个核心簇，它们具有更紧密的网络结构和更强的表达相关性。具体来说，系统地描绘了多个层次的分子特征，包括五个核心簇中基因的体细胞突变、拷贝数变异和 DNA 甲基化。我们发现，这些基因在这五个核心簇中的表达和甲基化水平上表现出很强的相关性。这五个核心簇可能成为 KIRC 的特殊预后生物标志物，功能分析表明它们与免疫和炎症系统的激活以及癌症进展有关。
我们的研究结果强调了免疫和炎症基因在 KIRC 中的新作用。
