Dataset Information

The prognostic value of CYP2C subfamily genes in hepatocellular carcinoma.

ABSTRACT: Cytochrome P2C (CYP2C) subfamily members (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) are known to participate in clinical drug metabolism. However, the association between CYP2C subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP2C subfamily gene expression levels with HCC prognosis. Data of 360 HCC patients in The Cancer Genome Atlas database and 231 in the Gene Expression Omnibus database were analyzed. Kaplan-Meier analysis and a Cox regression model were used to ascertain overall survival and recurrence-free survival, and to calculate median survival time using hazard ratios (HR) and 95% confidence intervals (CI). In TCGA database, low expression of CYP2C8, CYP2C9, and CYP2C19 in tumor tissue was associated with a short median survival time (all crude P = 0.001, adjusted P = 0.004, P = 0.047, and P = 0.020, respectively). In TCGA database, joint effects analysis of the combinations of CYP2C8 and CYP2C9, CYP2C8 and CYP2C19, and CYP2C9 and CYP2C19 revealed that high expression of two genes (group 4; group IV, group d) was associated with a reduced risk of death as compared to low expression (group 1, group I, and group a) (adjusted P = 0.005, P = 0.013, and P = 0.016, respectively). In TCGA database, joint effects analysis of CYP2C8, CYP2C9, and CYP2C19 showed that the risk of death from HCC was lower for groups C and D than for group A (adjusted P = 0.012 and P = 0.008, respectively). CYP2C8, CYP2C9, and CYP2C19 gene expression levels are potential prognostic markers of HCC following hepatectomy.

SUBMITTER: Wang X

PROVIDER: S-EPMC5911570 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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The prognostic value of CYP2C subfamily genes in hepatocellular carcinoma.

Wang Xiangkun X Yu Tingdong T Liao Xiwen X Yang Chengkun C Han Chuangye C Zhu Guangzhi G Huang Ketuan K Yu Long L Qin Wei W Su Hao H Liu Xiaoguang X Peng Tao T

Cancer medicine 20180226 4

Cytochrome P2C (CYP2C) subfamily members (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) are known to participate in clinical drug metabolism. However, the association between CYP2C subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP2C subfamily gene expression levels with HCC prognosis. Data of 360 HCC patients in The Cancer Genome Atlas database and 231 in the Gene Expression Omnibus database were analyzed. Kaplan-Meier analysis and ...[more]

PMID: 29479826

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Project description:Background: A high mortality rate makes hepatocellular carcinoma (HCC) one of the most common types of cancer globally. 5-methylcytosine (m5C) is an epigenetic modification that contributes to the prognosis of several cancers, but its relevance to HCC remains unknown. We sought to determine if the m5C-related regulators had any diagnostic or prognostic value in HCC. Methods: M5C regulatory genes were screened and compared between HCC and normal tissue from The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. Least absolute shrinkage and selection operator method (LASSO) and univariate Cox regression analysis of differentially expressed genes were then performed to identify diagnostic markers. A LASSO prognostic model was constructed using M5C regulatory genes with prognostic values screened by TCGA expression data. HCC patients were stratified based on risk score, then clinical characteristics analysis and immune correlation analysis were performed for each subgroup, and the molecular functions of different subgroups were analyzed using both Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). The prognostic model was evaluated using univariate and multivariate Cox analyses as well as a nomogram. Molecular typing was performed according to m5C regulatory genes and immune checkpoint genes expression respectively, and clinical characterization and immune correlation analysis were performed for each subgroup. Results: M5C regulatory genes are expressed differently in HCC patients with different clinical and pathological characteristics, and mutations in these genes are frequent. Based on five m5C regulators (NOP2, NSUN2, TET1, YBX1, and DNMT3B), we constructed a prognostic model with high predictive ability. The risk score was found to be an independent prognostic indicator. Additionally, risk scores can also be applied in subgroups with different clinical characteristics as prognostic indicators. Conclusion: The study combined data from TCGA and GEO for the first time to reveal the genetic and prognostic significance of m5C-related regulators in HCC, which provides new directions for identifying predictive biomarkers and developing molecularly targeted therapies for HCC.

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Dataset Information

The prognostic value of CYP2C subfamily genes in hepatocellular carcinoma.

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The prognostic value of CYP2C subfamily genes in hepatocellular carcinoma.

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