通过综合生物信息学分析鉴定结肠炎相关结肠癌的枢纽基因和通路。

Identification of hub genes and pathways in colitis-associated colon cancer by integrated bioinformatic analysis.

机构信息

Department of General Surgery, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, 272000, Shandong Province, China.

Key Laboratory of Precision Oncology in Universities of Shandong, Department of Pathology and Institute of Precision Medicine, Taibai Lake New Area, Jining Medical University, 133 Hehua Road, Jining, 272067, Shandong Province, China.

出版信息

BMC Genom Data. 2022 Jun 22;23(1):48. doi: 10.1186/s12863-022-01065-7.

BACKGROUND

Colitis-associated colon cancer (CAC) patients have a younger age of onset, more multiple lesions and invasive tumors than sporadic colon cancer patients. Early detection of CAC using endoscopy is challenging, and the incidence of septal colon cancer remains high. Therefore, identifying biomarkers that can predict the tumorigenesis of CAC is in urgent need.

RESULTS

A total of 275 DEGs were identified in CAC. IGF1, BMP4, SPP1, APOB, CCND1, CD44, PTGS2, CFTR, BMP2, KLF4, and TLR2 were identified as hub DEGs, which were significantly enriched in the PI3K-Akt pathway, stem cell pluripotency regulation, focal adhesion, Hippo signaling, and AMPK signaling pathways. Sankey diagram showed that the genes of both the PI3K-AKT signaling and focal adhesion pathways were upregulated (e.g., SPP1, CD44, TLR2, CCND1, and IGF1), and upregulated genes were predicted to be regulated by the crucial miRNAs: hsa-mir-16-5p, hsa-mir-1-3p, et al. Hub gene-TFs network revealed FOXC1 as a core transcription factor. In ulcerative colitis (UC) patients, KLF4, CFTR, BMP2, TLR2 showed significantly lower expression in UC-associated cancer. BMP4 and IGF1 showed higher expression in UC-Ca compared to nonneoplastic mucosa. Survival analysis showed that the differential expression of SPP1, CFRT, and KLF4 were associated with poor prognosis in colon cancer.

CONCLUSION

Our study provides novel insights into the mechanism underlying the development of CAC. The hub genes and signaling pathways may contribute to the prevention, diagnosis and treatment of CAC.

背景

结肠炎相关结肠癌（CAC）患者的发病年龄比散发性结肠癌患者年轻，病变和侵袭性肿瘤更多。使用内窥镜早期发现 CAC 具有挑战性，间隔性结肠癌的发病率仍然很高。因此，迫切需要确定可预测 CAC 肿瘤发生的生物标志物。

结果

在 CAC 中鉴定出 275 个差异表达基因。IGF1、BMP4、SPP1、APOB、CCND1、CD44、PTGS2、CFTR、BMP2、KLF4 和 TLR2 被鉴定为枢纽 DEG，这些基因在 PI3K-Akt 通路、干细胞多能性调节、黏附斑、Hippo 信号通路和 AMPK 信号通路中显著富集。Sankey 图显示，PI3K-AKT 信号通路和黏附斑通路的基因均上调（例如 SPP1、CD44、TLR2、CCND1 和 IGF1），上调的基因被预测受关键 miRNA 调控：hsa-mir-16-5p、hsa-mir-1-3p 等。枢纽基因-TF 网络显示 FOXC1 是一个核心转录因子。在溃疡性结肠炎（UC）患者中，KLF4、CFTR、BMP2、TLR2 在 UC 相关癌症中的表达明显降低。与非肿瘤黏膜相比，BMP4 和 IGF1 在 UC-Ca 中表达更高。生存分析表明，SPP1、CFTR 和 KLF4 的差异表达与结肠癌预后不良相关。