Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, China.
Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, China.
Pharmacol Res. 2020 Oct;160:105087. doi: 10.1016/j.phrs.2020.105087. Epub 2020 Jul 16.
Distant metastasis is the main cause of death in patients with colon-adenocarcinoma(COAD). Due to the lack of effective molecular markers and treatment, the prognosis of patients with metastatic colon cancer is still rather poor.
Metastatic related signature (MRS) of stage I and stage IV in colon cancer were identified from different cohorts. Univariate cox regression is used to analyze the relationship between MRS and the overall survival. L1000FWD and DGIdb databases are used to identify molecular drugs. Expression and functional experimental validation of the hub MRS were carried out.
16 MRS were identified, of which 14 MRS was significantly correlated with overall survival. Further functional enrichment analysis showed that MRS was significantly involved with important biological functions such as cell migration, and apoptosis. As important metastatic related genes, GSR, FAS and CYP1B1 have significant interaction with drug molecules. Further studies have confirmed that the expression of FAS and GSR is low, and inhibition of its expression can promote the metastasis of COAD. CYP1B1 expression is highly expressed, and inhibition of its expression can attenuate the malignant biological behavior of colon cancer.
Our research could increase the understanding of the mechanism of colon cancer metastasis and provide theoretical basis for the treatment of metastatic colon cancer.
远处转移是结直肠腺癌（COAD）患者死亡的主要原因。由于缺乏有效的分子标志物和治疗方法，转移性结直肠癌患者的预后仍然相当差。
从不同队列中鉴定出 I 期和 IV 期结直肠癌的转移相关特征（MRS）。单因素 cox 回归分析 MRS 与总生存期的关系。利用 L1000FWD 和 DGIdb 数据库鉴定分子药物。对关键 MRS 的表达和功能进行实验验证。
鉴定出 16 个 MRS，其中 14 个 MRS 与总生存期显著相关。进一步的功能富集分析表明，MRS 与细胞迁移和细胞凋亡等重要生物学功能显著相关。作为重要的转移相关基因，GSR、FAS 和 CYP1B1 与药物分子具有显著的相互作用。进一步的研究证实，FAS 和 GSR 的表达水平较低，抑制其表达可促进 COAD 的转移。CYP1B1 表达水平较高，抑制其表达可减弱结肠癌的恶性生物学行为。
我们的研究可以加深对结直肠癌转移机制的理解，并为转移性结直肠癌的治疗提供理论依据。
