Liu Wei-Qing, Li Wen-Liang, Ma Shu-Min, Liang Lei, Kou Zhi-Yong, Yang Jun
Department of Internal Medicine-Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, PR China.
Department of Oncology, First Affiliated Hospital of Kunming Medical University, No. 295 Xichang road, Kunming, Yunnan 650032, PR China.
Transl Oncol. 2021 Mar;14(3):101011. doi: 10.1016/j.tranon.2021.101011. Epub 2021 Jan 13.
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.
在本研究中，我们旨在基于两个基因表达综合数据库（GEO）数据集，揭示驱动结直肠癌（CRC）肝转移发病机制的基因，并识别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。我们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（DEG）。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CRC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CRC肝转移相关的关键免疫特征基因集，其中通过蛋白质-蛋白质相互作用（PPI）网络筛选出两个被确定为关键DEG的关键免疫基因家族（CD和CCL）。这些基因家族中的一些成员与CRC的两种亚型即结肠腺癌（COAD）和直肠腺癌（READ）的无病生存期（DFS）或总生存期（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、白细胞增殖和趋化性密切相关。这些结果对于理解CRC肝转移的发病机制具有重要价值，对于理解免疫肿瘤浸润在CRC中的作用也具有至关重要的意义。我们的研究还确定了CRC肝转移的潜在有效治疗靶点，包括CCL20、CCL24和CD70。
