Identification of Hub Genes Associated With Sensitivity of 5-Fluorouracil Based Chemotherapy for Colorectal Cancer by Integrated Bioinformatics Analysis.

Identification of Hub Genes Associated With Sensitivity of 5-Fluorouracil Based Chemotherapy for Colorectal Cancer by Integrated Bioinformatics Analysis.
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DOI:
10.3389/fonc.2021.604315
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发表时间:
2021
影响因子:
4.7
通讯作者:
Fu K
Fu K
中科院分区:
医学3区
文献类型:
--
作者:
Wang Y;Wei Q;Chen Y;Long S;Yao Y;Fu K

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结直肠癌是最常见的恶性肿瘤之一。5-氟尿嘧啶(5-FU)已用于CRC患者的标准一线治疗数十年。虽然5-FU为主的化疗提高了结直肠癌患者的总生存率,但结直肠癌对5-FU为主的化疗耐药是导致治疗失败的主要原因。因此,迫切需要鉴定新的生物标志物来预测对基于5-FU的化疗的反应。在本研究中,GSE 3964的基因表达谱从基因表达Omnibus数据库中被用来探索潜在的基因相关的内在耐药5-FU。使用加权基因共表达网络分析(WGCNA)发现包含81个基因的基因模块与化疗反应具有最高的相关性。然后构建蛋白质-蛋白质相互作用(PPI)网络,并利用Cytoscape的CytoHubba插件鉴定10个枢纽基因(TGFBI、NID、LEPREL 2、COL 11 A1、CYR 61、PCOLCE、IGFBP 7、COL 4A 2、CSPG 2和VTN)。这些枢纽基因中有7个在化疗敏感和化疗耐药样品之间的表达显示出显著差异。使用TCGA COAD(结直肠腺癌)数据评估这7个基因的预后价值。结果表明,TGFBI在化疗敏感患者中高表达,且TGFBI高表达的患者具有更好的生存期。
Colorectal cancer (CRC) is one of the most common malignant tumors. 5-fluorouracil (5-FU) has been used for the standard first-line treatment for CRC patients for several decades. Although 5-FU based chemotherapy has increased overall survival (OS) of CRC patients, the resistance of CRC to 5-FU based chemotherapy is the principal cause for treatment failure. Thus, identifying novel biomarkers to predict response to 5-FU based chemotherapy is urgently needed. In the present study, the gene expression profile of GSE3964 from the Gene Expression Omnibus database was used to explore the potential genes related to intrinsic resistance to 5-FU. A gene module containing 81 genes was found to have the highest correlation with chemotherapy response using Weighted Gene Co-expression Network Analysis (WGCNA). Then a protein-protein interaction (PPI) network was constructed and ten hub genes (TGFBI, NID, LEPREL2, COL11A1, CYR61, PCOLCE, IGFBP7, COL4A2, CSPG2, and VTN) were identified using the CytoHubba plugin of Cytoscape. Seven of these hub genes showed significant differences in expression between chemotherapy-sensitive and chemotherapy-resistant samples. The prognostic value of these seven genes was evaluated using TCGA COAD (Colorectal Adenocarcinoma) data. The results showed that TGFBI was highly expressed in chemotherapy-sensitive patients, and patients with high TGFBI expression have better survival.
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