Qi Lu, Ding Yanqing
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Oncotarget. 2017 Dec 27;9(5):6086-6094. doi: 10.18632/oncotarget.23710. eCollection 2018 Jan 19.
There are many stages in the development and metastasis of colorectal cancer (CRC). In this study, we compared the differential expression genes in different stages of metastatic CRC. Then, we screened the continuously up-regulated genes and the continuously down-regulated genes that were associated with the development and metastasis of CRC. After analyzing the intersection of differential expression genes in each stage, we screened the continuously up-regulated genes and deviated genes in the extracellular matrix and the continuously down-regulated genes and deviated genes in the mitochrondia of CRC. Then, we performed gene ontology enrichment analysis of the deviated genes in different phases, and we found that key molecular events occurred in the period extending from stage II to III (early stage of metastasis) of CRC. Furthermore, in this period we found that the chemotaxis of inflammatory cells had decreased in the extracellular matrix. On the other hand, the aerobic respiration had increased in the mitochondrion. Then, we constructed protein-protein interaction network of deviated genes in the extracellular matrix and mitochondrion. We used the network module and hub network to analyze the protein-protein interaction network. The network module analysis showed that the protein complex of VEGFA and CCL7-CCR3 is the key node in the extracellular matrix, while MAPK1 is the key node in the mitochondrion. The hub network analysis showed that the signal transmission chain FN1→SPARC→COL1A1→MMP2 is the key regulatory pathway for extracellular signal transmission. Furthermore, it also showed that CAV1→MAPK3→RAF1→NR3C1→MAPK1→ESR1 is the key regulatory pathway for signal transmission in mitochondrion.
结直肠癌（CRC）的发展和转移有许多阶段。在本研究中，我们比较了转移性CRC不同阶段的差异表达基因。然后，我们筛选了与CRC发展和转移相关的持续上调基因和持续下调基因。在分析每个阶段差异表达基因的交集后，我们筛选了CRC细胞外基质中持续上调基因和偏离基因以及线粒体中持续下调基因和偏离基因。然后，我们对不同阶段的偏离基因进行了基因本体富集分析，发现关键分子事件发生在CRC从II期到III期（转移早期）的阶段。此外，在此期间我们发现细胞外基质中炎症细胞的趋化性降低。另一方面，线粒体中的有氧呼吸增加。然后，我们构建了细胞外基质和线粒体中偏离基因的蛋白质-蛋白质相互作用网络。我们使用网络模块和枢纽网络分析蛋白质-蛋白质相互作用网络。网络模块分析表明，VEGFA和CCL7-CCR3的蛋白质复合物是细胞外基质中的关键节点，而MAPK1是线粒体中的关键节点。枢纽网络分析表明，信号传导链FN1→SPARC→COL1A1→MMP2是细胞外信号传导的关键调节途径。此外，它还表明CAV1→MAPK3→RAF1→NR3C1→MAPK1→ESR1是线粒体中信号传导的关键调节途径。
