结直肠癌新型诊断和预后生物标志物：能够克服异质性特异性障碍，适用于全球应用。
Novel diagnostic and prognostic biomarkers of colorectal cancer: Capable to overcome the heterogeneity-specific barrier and valid for global applications.
机构信息
Department of Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.
出版信息
PLoS One. 2021 Sep 2;16(9):e0256020. doi: 10.1371/journal.pone.0256020. eCollection 2021.
INTRODUCTION
The heterogeneity-specific nature of the available colorectal cancer (CRC) biomarkers is significantly contributing to the cancer-associated high mortality rate worldwide. Hence, this study was initiated to investigate a system of novel CRC biomarkers that could commonly be employed to the CRC patients and helpful to overcome the heterogenetic-specific barrier.
METHODS
Initially, CRC-related hub genes were extracted through PubMed based literature mining. A protein-protein interaction (PPI) network of the extracted hub genes was constructed and analyzed to identify few more closely CRC-related hub genes (real hub genes). Later, a comprehensive bioinformatics approach was applied to uncover the diagnostic and prognostic role of the identified real hub genes in CRC patients of various clinicopathological features.
RESULTS
Out of 210 collected hub genes, in total 6 genes (CXCL12, CXCL8, AGT, GNB1, GNG4, and CXCL1) were identified as the real hub genes. We further revealed that all the six real hub genes were significantly dysregulated in colon adenocarcinoma (COAD) patients of various clinicopathological features including different races, cancer stages, genders, age groups, and body weights. Additionally, the dysregulation of real hub genes has shown different abnormal correlations with many other parameters including promoter methylation, overall survival (OS), genetic alterations and copy number variations (CNVs), and CD8+T immune cells level. Finally, we identified a potential miRNA and various chemotherapeutic drugs via miRNA, and real hub genes drug interaction network that could be used in the treatment of CRC by regulating the expression of real hub genes.
CONCLUSION
In conclusion, we have identified six real hub genes as potential biomarkers of CRC patients that could help to overcome the heterogenetic-specific barrier across different clinicopathological features.
简介
现有的结直肠癌（CRC）生物标志物具有异质性特异性，这极大地导致了全球癌症相关的高死亡率。因此，本研究旨在探索一种新型 CRC 生物标志物系统，该系统可以普遍应用于 CRC 患者，有助于克服异质性特异性障碍。
方法
首先，通过基于 PubMed 的文献挖掘提取与 CRC 相关的枢纽基因。构建并分析提取的枢纽基因的蛋白质-蛋白质相互作用（PPI）网络，以识别更多与 CRC 密切相关的枢纽基因（真正的枢纽基因）。然后，应用综合生物信息学方法来揭示鉴定出的真正枢纽基因在具有各种临床病理特征的 CRC 患者中的诊断和预后作用。
结果
在收集的 210 个枢纽基因中，总共鉴定出 6 个基因（CXCL12、CXCL8、AGT、GNB1、GNG4 和 CXCL1）为真正的枢纽基因。我们进一步揭示，所有这六个真正的枢纽基因在各种临床病理特征（包括不同种族、癌症阶段、性别、年龄组和体重）的结肠腺癌（COAD）患者中均显著失调。此外，真正的枢纽基因的失调显示出与许多其他参数的不同异常相关性，包括启动子甲基化、总生存期（OS）、遗传改变和拷贝数变异（CNVs）以及 CD8+T 免疫细胞水平。最后，我们通过 miRNA 和真正的枢纽基因药物相互作用网络，鉴定了一种潜在的 miRNA 和各种化疗药物，这些药物可以通过调节真正的枢纽基因的表达，用于 CRC 的治疗。
结论
总之，我们已经确定了六个真正的枢纽基因作为 CRC 患者的潜在生物标志物，这些标志物可以帮助克服不同临床病理特征下的异质性特异性障碍。
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