Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
Int J Mol Med. 2018 Jul;42(1):368-380. doi: 10.3892/ijmm.2018.3631. Epub 2018 Apr 18.
Inflammatory genes serve a crucial role in the pathogenesis of inflammation‑associated tumors. However, as recent studies have mainly focused on the effects of single inflammatory genes on colorectal cancer (CRC), but not on the global interactions between genes, the underlying mechanisms between inflammatory genes and CRC remain unclear. In the current study, two inflammation‑associated networks were constructed based on inflammatory genes, differentially expressed genes (DEGs) in CRC vs. normal samples, and protein‑protein interactions (PPIs). These networks included an inflammation‑related neighbor network (IRNN) and an inflammation‑related DEG network (IRDN). Notably, the results indicated that the inflammatory genes served as important CRC‑associated genes in the IRNN. Certain inflammatory genes were more likely to be network hubs and exhibited higher betweenness centralities, indicating that these inflammatory hub genes had central roles in the communication between genes in the IRNN. By contrast, in the IRDN, functional enrichment analysis revealed that genes were enriched in numerous cancer‑associated functions and pathways. Subsequently, 14 genes in a module were identified in the IRDN as the potential biomarkers associated with disease‑free survival (DFS) in CRC patients in the GSE24550 dataset, the prognosis of which was further validated using three independent datasets (GSE24549, GSE34551 and GSE103479). All 14 genes (including BCAR1, CRK, FYN, GRB2, LCP2, PIK3R1, PLCG1, PTK2, PTPN11, PTPN6, SHC1, SOS1, SRC and SYK) in this module were inflammatory genes, emphasizing the critical role of inflammation in CRC. In conclusion, these findings based on integrated inflammation‑associated networks provided a novel insight that may help elucidate the inflammation‑mediated mechanisms involved in CRC.
炎症基因在炎症相关肿瘤的发病机制中起着至关重要的作用。然而，由于最近的研究主要集中在单个炎症基因对结直肠癌（CRC）的影响上，而不是基因之间的整体相互作用，因此炎症基因与 CRC 之间的潜在机制仍不清楚。在本研究中，基于炎症基因、CRC 与正常样本之间差异表达的基因（DEGs）和蛋白质-蛋白质相互作用（PPIs）构建了两个炎症相关网络，包括一个炎症相关邻近网络（IRNN）和一个炎症相关 DEG 网络（IRDN）。值得注意的是，结果表明，炎症基因在 IRNN 中作为重要的 CRC 相关基因。某些炎症基因更有可能成为网络枢纽，并表现出较高的介数中心度，表明这些炎症枢纽基因在 IRNN 中基因之间的通讯中发挥着核心作用。相比之下，在 IRDN 中，功能富集分析表明，基因在许多癌症相关功能和途径中富集。随后，在 IRDN 中确定了一个模块中的 14 个基因作为与 GSE24550 数据集 CRC 患者无病生存（DFS）相关的潜在生物标志物，并用三个独立数据集（GSE24549、GSE34551 和 GSE103479）进一步验证了这些基因的预后。该模块中的所有 14 个基因（包括 BCAR1、CRK、FYN、GRB2、LCP2、PIK3R1、PLCG1、PTK2、PTPN11、PTPN6、SHC1、SOS1、SRC 和 SYK）均为炎症基因，强调了炎症在 CRC 中的关键作用。总之，这些基于整合炎症相关网络的研究结果提供了一个新的视角，可能有助于阐明 CRC 中涉及的炎症介导机制。
