Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
Department of Oncology and Hematology Surgery, China-Japan Union Hospital, Changchun, Jilin Province, China.
Cell Cycle. 2021 Apr;20(8):781-791. doi: 10.1080/15384101.2021.1903208. Epub 2021 Mar 28.
Colorectal cancer (CRC) is one of the most common cancer, and the early detection of CRC is essential to improve the survival rate of patients. To identify diagnostic markers for colorectal cancer (CRC) by screening differentially expressed proteins (DEPs) in CRC. The DEPs were initially obtained from 12 CRC samples and 12 healthy control samples, and verification analysis was performed in another 34 CRC samples and 34 normal controls. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment with DEPs was analyzed by the R package clusterProfiler (Version 3.2.11), and the DEP-associated protein-protein interaction (PPI) network was created from the STRING database. Additionally, Support Vector Machine (SVM) model prediction and survival analyses were conducted on the key DEPs. Preliminary screening and functional analysis showed that the DEPs mainly overrepresented in pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, Rap1, Ras, and MAPK signaling pathways. The key DEPs, including AgRP, ANG-2, Dtk, EOT3, FGF-4, FGF-9, HCC-4, IL-16, IL-8, MIF, MSPa, TECK, TPO, TRAIL R3, and VEGF-D, were used to construct a custom chip. The drug-gene interaction network suggested that TPO was a key drug target. ROC curve showed the SVM diagnostic model with the DEPs IL-8, MSPa, MIF, FGF-9, ANG-2, and AgRP had better diagnostic performance with an AUC of 0.933. Survival analysis showed the expression of FGF9, TPO, TRAIL R3, Dtk, TECK and FGF4 were associated with prognosis. This study revealed the important serum proteins in the pathogenesis of CRC, which might serve as useful and noninvasive predictors for the diagnosis of CRC.
结直肠癌（CRC）是最常见的癌症之一，早期发现 CRC 对于提高患者的生存率至关重要。通过筛选 CRC 中差异表达的蛋白质（DEPs）来鉴定结直肠癌（CRC）的诊断标志物。首先从 12 例 CRC 样本和 12 例健康对照样本中获得 DEPs，并在另外 34 例 CRC 样本和 34 例正常对照样本中进行验证分析。使用 R 包 clusterProfiler（版本 3.2.11）对 DEPs 进行京都基因与基因组百科全书（KEGG）通路富集分析，并从 STRING 数据库创建 DEP 相关的蛋白质-蛋白质相互作用（PPI）网络。此外，对关键 DEPs 进行支持向量机（SVM）模型预测和生存分析。初步筛选和功能分析表明，DEPs 主要在细胞因子-细胞因子受体相互作用、趋化因子信号通路、Rap1、Ras 和 MAPK 信号通路等途径中过表达。关键 DEPs，包括 AgRP、ANG-2、Dtk、EOT3、FGF-4、FGF-9、HCC-4、IL-16、IL-8、MIF、MSPa、TECK、TPO、TRAIL R3 和 VEGF-D，用于构建定制芯片。药物-基因相互作用网络表明 TPO 是一个关键的药物靶点。ROC 曲线显示，基于 DEPs IL-8、MSPa、MIF、FGF-9、ANG-2 和 AgRP 的 SVM 诊断模型具有更好的诊断性能，AUC 为 0.933。生存分析表明，FGF9、TPO、TRAIL R3、Dtk、TECK 和 FGF4 的表达与预后相关。本研究揭示了结直肠癌发病机制中的重要血清蛋白，它们可能作为 CRC 诊断的有用且非侵入性预测指标。
