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细胞色素P450 3A亚家族成员差异表达对肝细胞癌的预后价值

The prognostic value of differentially expressed CYP3A subfamily members for hepatocellular carcinoma.

作者信息

Yu Tingdong, Wang Xiangkun, Zhu Guangzhi, Han Chuangye, Su Hao, Liao Xiwen, Yang Chengkun, Qin Wei, Huang Ketuan, Peng Tao

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China,

出版信息

Cancer Manag Res. 2018 Jun 25;10:1713-1726. doi: 10.2147/CMAR.S159425. eCollection 2018.

DOI:10.2147/CMAR.S159425
PMID:29983591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6025769/
Abstract

OBJECTIVE

The activities of four cytochrome P3A (CYP3A) subfamily members (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) are well documented in drug metabolism. However, the association between CYP3A subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP3A subfamily mRNA expression levels with HCC prognosis.

MATERIALS AND METHODS

Data from a total of 360 HCC patients were retrieved from The Cancer Genome Atlas database, and data from 231 HCC patients were retrieved from the Gene Expression Omnibus database. Kaplan-Meier analysis and Cox regression models were utilized to determine median survival, overall survival, and recurrence-free survival. Hazard ratios and 95% CI were calculated.

RESULTS

Low expression of , , and in the tumor tissue was associated with short median survival (crude =0.004, 0.001, and 0.001; adjusted =0.022, 0.005, and 0.013, respectively). Joint-effects combination analysis of /, /, and revealed that high expression groups of two genes (group C, group c, group 3) were associated with a reduced risk of death, as compared to low expression of two genes (group A, group a, group 1), and the adjusted values were 0.001, 0.004, and 0.001, respectively. Joint-effects analysis of , , and showed that groups III and IV had a reduced risk of death, as compared to group I (adjusted =0.024 and 0.002, respectively).

CONCLUSION

, , and mRNA expression levels are potential prognostic markers of HCC.

摘要

目的

四种细胞色素P3A（CYP3A）亚家族成员（CYP3A4、CYP3A5、CYP3A7和CYP3A43）在药物代谢中的活性已有充分记录。然而，CYP3A亚家族成员与肝细胞癌（HCC）之间的关联仍不清楚。本研究调查了CYP3A亚家族mRNA表达水平对HCC预后的预测价值。

材料与方法

从癌症基因组图谱数据库中检索了总共360例HCC患者的数据，并从基因表达综合数据库中检索了231例HCC患者的数据。采用Kaplan-Meier分析和Cox回归模型来确定中位生存期、总生存期和无复发生存期。计算风险比和95%置信区间。

结果

肿瘤组织中 、 和 的低表达与较短的中位生存期相关（粗风险比分别为0.004、0.001和0.001；调整后分别为0.022、0.005和0.013）。 /、 /和 的联合效应组合分析显示，与两个基因的低表达组（A组、a组、1组）相比，两个基因的高表达组（C组、c组、3组）死亡风险降低，调整后的风险比值分别为0.001、0.004和0.001。 、 和 的联合效应分析显示，与I组相比，III组和IV组死亡风险降低（调整后的风险比值分别为0.024和0.002）。

结论

、 和 的mRNA表达水平是HCC潜在的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/a8bb0adfa94e/cmar-10-1713Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/220199ac0fc4/cmar-10-1713Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/acc032ded008/cmar-10-1713Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/dc04436e6f57/cmar-10-1713Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/04af3821dd7c/cmar-10-1713Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/0ffde353289b/cmar-10-1713Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/a8bb0adfa94e/cmar-10-1713Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/220199ac0fc4/cmar-10-1713Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/acc032ded008/cmar-10-1713Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/dc04436e6f57/cmar-10-1713Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/04af3821dd7c/cmar-10-1713Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/0ffde353289b/cmar-10-1713Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/696f/6025769/a8bb0adfa94e/cmar-10-1713Fig6.jpg

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