Discovery of core gene families associated with liver metastasis in colorectal cancer and regulatory roles in tumor cell immune infiltration.
Discovery of core gene families associated with liver metastasis in colorectal cancer and regulatory roles in tumor cell immune infiltration.
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结直肠癌肝转移相关核心基因家族的发现及其在肿瘤细胞免疫浸润中的调控作用
DOI：
10.1016/j.tranon.2021.101011
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发表时间：
2021-03
影响因子：
5
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Liu WQ;Li WL;Ma SM;Liang L;Kou ZY;Yang J
我们从GSE75050数据集中鉴定出1608个基因片段（690个上调，918个下调）。上调的SERPINB3和SERPINB4基因属于内源性蛋白酶抑制剂家族。下调的DEFA5和DEFA6基因对结肠癌具有抗病毒活性。我们进一步筛选了44个属于CCL、CD和CXCL家族基因的deg。CCL、CD和CXCL家族可能与免疫肿瘤浸润有关。在本研究中，我们旨在揭示驱动结直肠癌（CRC）肝转移发病机制的基因，并基于两个GEO数据集确定可作为治疗结直肠癌肝转移患者潜在治疗靶点的有效基因。实施了几种生物信息学方法。首先，差异表达分析在两个GEO数据集中筛选出关键的差异表达基因（DEGs）。基于基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析，我们确定了与结直肠癌肝转移相关的deg的富集功能和通路。其次，免疫浸润分析确定了与结直肠癌肝转移相关的关键免疫特征基因集，其中两个关键免疫基因家族（CD和CCL）被确定为关键deg，通过蛋白-蛋白相互作用（PPI）网络过滤。这些基因家族中的一些成员与两种CRC亚型（COAD和READ）的无病生存（DFS）或总生存（OS）相关。最后，对这两个基因家族及其邻近基因的功能富集分析表明，它们与细胞因子、白细胞增殖和趋化密切相关。这些结果对理解结直肠癌肝转移的发病机制具有重要价值，对理解肿瘤免疫浸润在结直肠癌中的作用具有重要意义。我们的研究还发现了包括CCL20、CCL24和CD70在内的CRC肝转移的潜在有效治疗靶点。
We identified 1608 DEGs (690 upregulated, 918 downregulated) from GSE75050 dataset. The upregulated SERPINB3 and SERPINB4 genes belong to endogenous protease inhibitor family. The downregulated DEFA5 and DEFA6 genes showed antiviral activity on colon carcinoma. We further screened 44 DEGs that belong to CCL, CD and CXCL family genes. CCL, CD, and CXCL families may contribute to immune tumor infiltration. In this study, we aimed to uncover genes that drive the pathogenesis of liver metastasis in colorectal cancer (CRC), and identify effective genes that could serve as potential therapeutic targets for treating with colorectal liver metastasis patients based on two GEO datasets. Several bioinformatics approaches were implemented. First, differential expression analysis screened out key differentially expressed genes (DEGs) across the two GEO datasets. Based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we identified the enrichment functions and pathways of the DEGs that were associated with liver metastasis in CRC. Second, immune infiltration analysis identified key immune signature gene sets associated with CRC liver metastasis, among which two key immune gene families (CD and CCL) identified as key DEGs were filtered by protein-protein interaction (PPI) network. Some of the members in these gene families were associated with disease free survival (DFS) or overall survival (OS) in two subtypes of CRC, namely COAD and READ. Finally, functional enrichment analysis of the two gene families and their neighboring genes revealed that they were closely associated with cytokine, leukocyte proliferation and chemotaxis. These results are valuable in comprehending the pathogenesis of liver metastasis in CRC, and are of seminal importance in understanding the role of immune tumor infiltration in CRC. Our study also identified potentially effective therapeutic targets for liver metastasis in CRC including CCL20, CCL24 and CD70.
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DOI：
10.1158/1078-0432.ccr-12-2940
发表时间：
2013-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chen C;Duckworth CA;Zhao Q;Pritchard DM;Rhodes JM;Yu LG
通讯作者：
Yu LG
影响因子：
168.9
作者：
Cunningham, David;Atkin, Wendy;Starling, Naureen
通讯作者：
Starling, Naureen
影响因子：
3.7
作者：
Borm, B;Requardt, RP;Kirfel, G
通讯作者：
Kirfel, G
影响因子：
7.5
作者：
Ge, Penglei;Wang, Weiwei;Wu, Yang
通讯作者：
Wu, Yang
DOI：
10.1007/1-4020-3764-3_12
发表时间：
2005-01-01
期刊：
GENOME INSTABILITY IN CANCER DEVELOPMENT
影响因子：
--
作者：
Debatisse, M;Malfoy, B
通讯作者：
Malfoy, B