李雅茹,卢秀荣,李锐彪,等.结直肠癌肝转移患者肠道菌群中肌苷单磷酸脱氢酶1的筛选及其临床意义[J].肿瘤学杂志,2023,29(10):860-868.
结直肠癌肝转移患者肠道菌群中肌苷单磷酸脱氢酶1的筛选及其临床意义
Screening of Inosine Monophosphate Dehydrogenase 1 in Intestinal Flora of Patients with Liver Metastasis from Colorectal Cancer and Its Clinical Significance
投稿时间:2023-05-22  
DOI:10.11735/j.issn.1671-170X.2023.10.B009
中文关键词:  结直肠肿瘤  肝转移  肠道菌群  肌苷单磷酸  肌苷单磷酸脱氢酶1
英文关键词:colorectal cancer  liver metastasis  intestinal flora  Inosine 5′-Monophosphate  inosine monophosphate dehydrogenase 1
基金项目:2019年河北省政府资助临床医学优秀人才培养项目
作者单位
李雅茹 河北北方学院附属第一医院 
卢秀荣 河北北方学院附属第一医院 
李锐彪 河北北方学院附属第一医院 
任成波 河北北方学院附属第一医院 
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中文摘要:
      摘 要:[目的] 探讨肠道菌群及其相关代谢物肌苷单磷酸脱氢酶1(inosine monophosphate dehydrogenase 1,IMPDH1)在结直肠癌(colorectal cancer ,CRC)肝转移中的临床意义。[方法] 选取CRC非肝转移(CRCNLM)及肝转移(CRCLM)患者各9例。采用16S rDNA测序检测患者粪便,采用液质联用技术检测微生物样本中的代谢物,并筛选出与肝转移相关的Inosine 5′-Monophoshpate。分析TCGA数据库CRC资料中IMPDH1的表达及其对临床预后的影响。[结果]与CRCNLM比较,P. Sphingomonas、F. Bacillus、A. Skermanella等在CRCLM患者中明显升高。经非靶向代谢组学和Tax4Fun功能富集分析,Inosine 5′-Monophosphate等在肝转移组中升高,且Inosine 5′-Monophoshpate与F. Bacillus呈正相关(r=0.564,P<0.05)。IMPDH1是Inosine 5′-Monophoshpate的关键代谢酶,在CRC及其肝转移患者中显著升高。根据ROC曲线的cut-off值(16.454 6)分为IMPDH1高低表达组,IMPDH1表达在CRC患者TNM分期组间差异具有统计学意义(P<0.05)。多因素结果显示,TNM分期(HR=1.041,95%CI:1.020~1.063)、IMPDH1表达(HR=1.007,95%CI:1.000~1.014)是影响CRC预后的独立风险因素(P<0.05)。随访11.69年后,IMPDH1高低表达患者的总生存率分别为15.2%和31.8%(P=0.01);随访6.86年后,在CRC肝转移患者中,IMPDH1高低表达患者的总生存率及1、3、5年生存率分别为0、59.2%、47.4%、0和12.3%、76.6%、58.5%、24.6%,差异有统计学意义(P=0.03)。[结论] F. Bacillus及其相关代谢物Inosine 5′-Monophoshpate的增加可能是导致CRC肝转移发生的原因之一,后者的关键酶IMPDH1高表达可能也是导致CRC预后差的风险因子。
英文摘要:
      Abstract:[Objective] To explore the clinical significance of intestinal flora and its related metabolite inosine monophosphate dehydrogenase 1(IMPDH1) in liver metastasis of colorectal cancer(CRC). [Methods] The 16S rDNA sequencing and liquid mass spectrometry were applied to screen metabolites of intestinal flora in feces samples from 9 colorectal cancer patients with liver metastasis and 9 colorectal cancer patients without liver metastasis. The screening results showed that Inosine 5′-Monophosphate might be associated with liver metastasis in CRC patients. The data of IMPDH1 expression and its influence on clinical prognosis in CRC patients were obtained from TCGA database and analyzed. [Results] Compared with CRC patients without liver metastasis, the proportions of P. Sphingomonas, F. Bacillus, and A. Skermanella were significantly increased in CRC patients with liver metastasis. Tax4Fun function prediction and non-targeted metabolomics analysis showed that the IMPDH1 and other metabolites were increased in the CRC patients with liver metastasis, and IMPDH1 was positively correlated with the abundance of F. Bacillus(r=0.564, P<0.05). As a key metabolic enzyme of Inosine 5′-Monophosphate, MPDH1 was significantly elevated in CRC patients with liver metastasis. According to the cut-off value of ROC(16.454 6), the CRC patients were divided into high and low expression groups of IMPDH1. The expression levels of IMPDH1 were significantly associated with TNM stages of CRC patients(P<0.05). Multivariate regression results showed that TNM stage(HR=1.041, 95%CI:1.020~1.063) and IMPDH1(HR=1.007, 95%CI:1.000~1.014) were independent risk factors for the prognosis of CRC patients(P<0.05). After 11.69-year follow-up, the survival of CRC patients with high and low expression of IMPDH1 were 15.2% and 31.8%, respectively(P=0.01). Follow-up for 6.86-year, the overall, 1, 3, 5-survival of liver metastasis patients with high and low expression of IMPDH1 were 0, 59.2%, 47.4%, 0 and 12.3%, 76.6%, 58.5%, 24.6%, respectively(P=0.03). [Conclusion] The increase of F. Bacillus abundance and its related metabolite Inosine 5′-Monophosphate may be associated with liver metastasis of CRC patients. The high expression of IMPDH1(a key metabolic enzyme of Inosine 5′-Monophosphate) may be a risk factor for poor prognosis of CRC patients.
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