An 8-gene predicting survival model of hepatocellular carcinoma (HCC) related to pyroptosis and cuproptosis

作者全名："Wang, Hongjin; Wang, Nian; Tang, Ze; Liu, Qiuyu; Nie, Shiyu; Tao, Wu"

作者地址："[Wang, Hongjin; Wang, Nian; Tang, Ze; Liu, Qiuyu; Nie, Shiyu; Tao, Wu] Chongqing Med Univ, Yongchuan Hosp, Dept Crit Care Med, Chongqing 402160, Peoples R China"

通信作者："Tao, W (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Dept Crit Care Med, Chongqing 402160, Peoples R China."

来源：HEREDITAS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001028728400001

JCR分区：Q3

影响因子：2.1

年份：2023

卷号：160

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Hepatocellular carcinoma; Prognostic model; Pyroptosis; Cuproptosis; Bioinformatics

摘要："BackgroundThe study aimed to establish a prognostic survival model with 8 pyroptosis-and-cuproptosis-related genes to examine the prognostic effect in patients of hepatocellular carcinoma (HCC).MethodsWe downloaded gene expression data and clinical information of HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). The clustering analysis and cox regression with LASSO were used for constructing an 8 PCmRNAs survival model. Using TCGA, ICGC and GEO cohort, the overall survival (OS) between high- and low- risk group was determined. We also evaluated independent prognostic indicators using univariate and multivariate analyses. The relatively bioinformatics analysis, including immune cell infiltration, function enrichment and drug sensitivity analyses, was performed as well. The gene expression of 8 PCmRNAs in vitro were validated in several HCC cell lines by qRT-PCR and Western blot. The relationship between GZMA and Fludarabine were further checked by CCK-8 assay.ResultsThe survival prognostic model was constructed with ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA using data from TCGA cohort. The ICGC and GEO cohort were used for model validation. Receiver operating characteristic (ROC) curves showed a good survival prediction by this model. Risk scores had the highest predictable value for survival among Stage, Age, Gender and Grade. Most Immune cells and immune functions were decreased in high-risk group. Besides, function enrichment analyses showed that steroid metabolic process, hormone metabolic process, collagen - containing extracellular matrix, oxidoreductase activity and pyruvate metabolism were enriched. Potential drugs targeted different PCDEGs like Nelarabine, Dexamethasone and Fludarabine were found as well. ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NOD1 were upregulated while NLRP6 and GZMA were downregulated in most HCC cell lines. The potential therapy of Fludarabine was demonstrated when GZMA was low expressed in Huh7 cell line.ConclusionWe constructed a novel 8-gene (ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA) prognostic model and explored potential functional information and microenvironment of HCC, which might be worthy of clinical application. In addition, several potential chemotherapy drugs were screened and Fludarabine might be effective for HCC patients whose GZMA was low expressed."

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