Complement C5 is a novel biomarker for liver metastasis of colorectal cancer.
Complement C5 is a novel biomarker for liver metastasis of colorectal cancer.
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补体C5是结直肠癌肝转移的新型生物标志物
DOI：
10.21037/jgo-22-829
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发表时间：
2022-10
影响因子：
2.1
通讯作者：
Guo, Lei
中科院分区：
文献类型：
--
作者：
Chang, Hulin;Jin, Lei;Xie, Peiyi;Zhang, Bo;Yu, Mincheng;Li, Hui;Liu, Shuang;Yan, Jiuliang;Zhou, Binghai;Li, Xiaoqiang;Xu, Yongfeng;Xiao, Yongsheng;Ye, Qinghai;Guo, Lei
关键词：
背景：结直肠癌是我国最常见的恶性肿瘤之一，发病率高，预后差。肝转移是结直肠癌患者死亡的主要原因。本研究旨在寻找准确的结直肠癌转移标志物，探讨结直肠癌肝转移的分子机制。方法从基因表达总表(GEO)数据库中筛选并下载3个独立的数据集。GEO2R工具用于确定结直肠癌组织和肝转移瘤组织中的差异表达基因(DEG)。接下来，使用注释、可视化和综合发现数据库(David)对基因本体论(GO)和京都基因和基因组百科全书(KEGG)进行了丰富分析。此外，使用检索相互作用基因(STRING)数据库的搜索工具Cytoscape和分子复合体检测(MCODE)分析了DEG的蛋白质-蛋白质相互作用(PPI)。然后，用UALCAN软件对目的基因在正常结肠和结直肠癌组织中的表达水平和Kaplan-Meier生存分析进行分析。用定量逆转录聚合酶链式反应(qRT-PCR)、Western印迹和免疫组织化学(IHC)检测目的基因在组织和细胞中的表达。体外研究目的基因对Coad细胞增殖、侵袭和迁移能力的影响。结果在三个独立的数据集中共发现92个共同的DEG。GO/KEGG分析表明，DEGS主要参与了14条不同的途径。蛋白质-蛋白质相互作用(PPI)网络显示，补体系统中C8A的上游基因C5(C5)与C8和其他关键HUB基因相关。同时，在线的UALCAN资源显示，C5在Coad样本中上调并促进了恶性进展。接下来，我们证实了C5对结直肠癌细胞株SW620和SW480的增殖、迁移和侵袭有显著的促进和促进作用。免疫组化检测显示，与配对的结直肠癌组织相比，C5在大多数LMCRC组织中也有高表达。结论我们的综合生物信息学研究结果表明，补体C5可能成为结直肠癌患者的潜在治疗靶点。
Background Colorectal cancer (CRC) is one of the most prominent malignant diseases, with a high incidence and a dismal prognosis. Metastasis to the liver is the leading cause of death in CRC patients. This study aimed to identify accurate metastatic biomarkers of CRC and investigate the potential molecular mechanisms of liver metastasis of colorectal cancer (LMCRC). Methods Three independent datasets were screened and downloaded from the Gene Expression Omnibus (GEO) database. The GEO2R tool was used to identify differentially expressed genes (DEGs) in CRC tissues and liver metastases. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Furthermore, the protein-protein interactions (PPIs) of the DEGs were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) database, Cytoscape, and Molecular Complex Detection (MCODE). Next, the expression levels and Kaplan-Meier survival analysis of the target gene between normal colon and CRC tissues were performed by UALCAN. The expression of the target gene in tissues and cell lines was verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry (IHC) assay. The impact of the target gene on the proliferation, invasion, and migration ability of COAD cells was explored in vitro. Results A total of 92 common DEGs were found in the three independent datasets. GO/KEGG enrichment analysis showed that the DEGs were mainly involved in 14 different pathways. The protein-protein interaction (PPI) network revealed that complement 5 (C5), the upstream gene of C8A in the complement system, was associated with C8 and other key hub genes. Meanwhile, the online UALCAN resource showed that C5 was up-regulated and facilitated malignant progression in COAD samples. Next, we confirmed that C5 remarkably increased and promoted cell proliferation, migration, and invasion in CRC cell lines, SW620 and SW480. The IHC assay showed C5 was also highly expressed in a majority of LMCRC tissues compared with paired CRC tissues. Conclusions The findings of our integrated bioinformatics study suggest that complement C5 might serve as a potential therapeutic target in patients with CRC.
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影响因子：
3.8
作者：
Chen C;Yi W;Zeng ZF;Wang QX;Jiang W;Gao YH;Chang H
通讯作者：
Chang H
影响因子：
2
作者：
Gu JN;Yao S;Cao YH;Deng SH;Mao FW;Jiang HY;He YT;Li XY;Ke SQ;Li HL;Li H;Liu XH;Liu HL;Wang JL;Wu K;Liu L;Cai KL
通讯作者：
Cai KL
影响因子：
16.6
作者：
Ishaque N;Abba ML;Hauser C;Patil N;Paramasivam N;Huebschmann D;Leupold JH;Balasubramanian GP;Kleinheinz K;Toprak UH;Hutter B;Benner A;Shavinskaya A;Zhou C;Gu Z;Kerssemakers J;Marx A;Moniuszko M;Kozlowski M;Reszec J;Niklinski J;Eils J;Schlesner M;Eils R;Brors B;Allgayer H
通讯作者：
Allgayer H
C3独立于C5驱动炎症性皮肤致癌。
DOI：
10.1016/j.jid.2020.06.025
发表时间：
2021-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Jackson WD;Gulino A;Fossati-Jimack L;Castro Seoane R;Tian K;Best K;Köhl J;Belmonte B;Strid J;Botto M
通讯作者：
Botto M
影响因子：
4
作者：
Kobayashi S;Takahashi S;Nomura S;Kojima M;Kudo M;Sugimoto M;Konishi M;Gotohda N;Taniguchi H;Yoshino T
通讯作者：
Yoshino T