Dataset Information

Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy.

ABSTRACT: Objective: The goal of our current study is to assess the immunohistochemical of p53, p21, nm23, and VEGF expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) prognosis after hepatectomy, as well as the prospective molecular mechanisms of prognostic indicator. Methods: There were 419 HBV-related HCC patients who were from southern China of Guangxi province and were used to evaluate the immunohistochemical expression for these biomarkers in prognosis. A genome-wide expression microarray dataset of HBV-related HCC were obtained from GSE14520. Results: In our study, the expression of p53, p21, and nm23 in cancer tissues of patients with hepatitis B-related hepatocellular carcinoma did not affected the clinical outcome of 2 years, 5 years or overall. Patients with high expression of VEGF had a worse overall survival after 2 years of surgery than patients with low expression (adjusted P=0.040, adjusted HR = 1.652, 95% CI = 1.024-2.665). Survival analysis of VEGF in GSE14520 cohort also demonstrated that VEGF mRNA expression also significantly associated with HBV-related HCC OS (adjusted P=0.035, adjusted HR =1.651, 95% CI =1.035-2.634). The prospective molecular mechanisms by co-expression analysis suggested that VEGF might be correlated to regulation of cell proliferation, cell growth and apoptotic process, Rap1 signaling pathway, HIF-1 signaling pathway, PPAR signaling pathway, cell cycle. Whereas the GSEA suggested that VEGF might involve in the regulation of HIF and HIF1A pathway, and TP53 regulation pathway. Conclusion: Our findings suggested that VEGF might be a prognostic indicator of HBV-related HCC, and we also identified the VEGF prospective molecular mechanisms through the whole genome co-expression and GSEA approaches.

SUBMITTER: Zhu GZ

PROVIDER: S-EPMC6959013 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy.

Zhu Guang-Zhi GZ Liao Xi-Wen XW Wang Xiang-Kun XK Gong Yi-Zhen YZ Liu Xiao-Guang XG Yu Long L Han Chuang-Ye CY Yang Cheng-Kun CK Su Hao H Huang Ke-Tuan KT Yu Ting-Dong TD Huang Jian-Lu JL Li Jia J Zeng Zhi-Ming ZM Qin Wei W Liu Zheng-Qian ZQ Zhou Xin X Liu Jun-Qi JQ Lu Lei L Han Quan-Fa QF Shang Li-Ming LM Ye Xin-Ping XP Peng Tao T

Journal of Cancer 20200101 4

<b>Objective:</b> The goal of our current study is to assess the immunohistochemical of p53, p21, nm23, and VEGF expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) prognosis after hepatectomy, as well as the prospective molecular mechanisms of prognostic indicator. <b>Methods:</b> There were 419 HBV-related HCC patients who were from southern China of Guangxi province and were used to evaluate the immunohistochemical expression for these biomarkers in prognosis. A genom ...[more]

PMID: 31949494

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Project description:BackgroundThe aim of our study was to evaluate the potential of expression and single nucleotide polymorphism of Acyl-CoA binding domain containing 4 (ACBD4) gene as prognosis biomarkers in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after hepatectomy.MethodsHBV-related HCC patients from the First Affiliated Hospital of Guangxi Medical University and GSE14520 were included in the current study, as well as The Cancer Genome Atlas (TCGA) HCC verification cohort. Prognostic analysis and multiple functional enrichment analysis methods were used to evaluate the prognostic value and potential biological functions of the ACBD4 gene in HBV-related HCC.ResultsWe found that ACBD4 gene is highly expressed in normal liver tissues and markedly down-regulated in HBV-related HCC tissues. ACBD4 gene was significantly related to overall survival (OS) of HCC in TCGA and GSE14520 cohorts, and patients with low ACBD4 expression were markedly related to poor OS. Rs4986172 was observed as an OS biomarker after hepatectomy in the Guangxi HBV-related HCC cohort. The OS of rs4986172 GG genotype was worse than that of HCC patients with A allele (AA and AG genotypes). Multifunctional enrichment analysis suggested that ACBD4 gene is closely related to the metabolic, peroxisome proliferator-activated receptor and cytochrome P450 pathway. Through connectivity map, we also identified eight compounds that may be used as targeted therapeutic agents for ACBD4 gene in HBV-related HCC; these compounds were scopoletin, alfaxalone, bephenium hydroxynaphthoate, apramycin, 4,5-dianilinophthalimide, DL-thiorphan, aminohippuric acid and quinidine. Immune microenvironment analysis revealed that there were significant differences in immune scores of HBV-related HCC tumor tissues with different ACBD4 expression levels.ConclusionOur study reveals that ACBD4 expression and rs4986172 can be serve as biomarkers of OS in HBV-related HCC patients after hepatectomy.

Project description:BackgroundHepatocellular carcinoma (HCC) is associated with a dismal prognosis, and prediction of the prognosis of HCC can assist in therapeutic decision-makings. An increasing number of studies have shown that the texture parameters of images can reflect the heterogeneity of tumors, and may have the potential to predict the prognosis of patients with HCC after surgical resection. The aim of this study was to investigate the prognostic value of computed tomography (CT) texture parameters in patients with HCC after hepatectomy and to develop a radiomics nomogram by combining clinicopathological factors and the radiomics signature.MethodsIn all, 544 eligible patients were enrolled in this retrospective study and were randomly divided into the training cohort (n = 381) and the validation cohort (n = 163). The tumor regions of interest (ROIs) were delineated, and the corresponding texture parameters were extracted. The texture parameters were selected by using the least absolute shrinkage and selection operator (LASSO) Cox model in the training cohort, and a radiomics signature was established. Then, the radiomics signature was further validated as an independent risk factor for overall survival (OS). The radiomics nomogram was established based on the Cox regression model. The concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to evaluate the performance of the radiomics nomogram.ResultsThe radiomics signature was formulated based on 7 OS-related texture parameters, which were selected in the training cohort. In addition, the radiomics nomogram was developed based on the following five variables: α-fetoprotein (AFP), platelet-to-lymphocyte ratio (PLR), largest tumor size, microvascular invasion (MVI) and radiomics score (Rad-score). The nomogram displayed good accuracy in predicting OS (C-index = 0.747) in the training cohort and was confirmed in the validation cohort (C-index = 0.777). The calibration plots also showed excellent agreement between the actual and predicted survival probabilities. The DCA indicated that the radiomics nomogram showed better clinical utility than the clinicopathologic nomogram.ConclusionThe radiomics signature is a potential prognostic biomarker of HCC after hepatectomy. The radiomics nomogram that integrated the radiomics signature can provide a more accurate estimation of OS than the clinicopathologic nomogram for HCC patients after hepatectomy.

Project description:BackgroundPredicting the long-term prognosis of individuals who experienced sorafenib treatment following partial hepatectomy due to hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is difficult. This work aims to create an effective prognostic nomogram for HBV related HCC patients who are receiving sorafenib treatment as adjuvant therapy after surgery.MethodsA total of 233 HBV-related HCC patients treated with or without sorafenib following partial hepatectomy at the Eastern Hepatobiliary Surgery Hospital from 2008 to 2013 were matched with propensity score matching analysis. The optimal cut-off point of the overall survival (OS) factor level was determined by x-tile. The selection of indicators was based on clinical findings. The Cox regression model with an interaction term was employed for evaluating the predictive value. Using a multivariate Cox proportional hazards model, a nomogram was subsequently formulated to analyze 111 patients treated with sorafenib. The nomogram's discriminative ability and predictive accuracy were determined using the concordance index (C-index), calibration, and ROC curve.ResultsThe matched sorafenib cohort of 111 patients and control cohort of 118 patients were analyzed. Subgroup analysis revealed that low GPC3, pERK, pAKT, serum AFP levels, without MVI, under 50 years old, male, TNM stage I/II and BCLC stage 0/A were significantly associated with a better OS in patients subjected to sorafenib treatment compared to those without sorafenib treatment after surgery. Multivariate analysis of the sorafenib cohort revealed GPC3, pERK, pAKT, serum AST, and BCLC stage as independent factors for OS, and all were included in the nomogram. The survival probability based on the calibration curve showed that the prediction of the nomogram was in good agreement with the actual observation. The C-index of the nomogram for predicting survival was 0.73(95% CI, 0.67-0.78). The area under the ROC curve (AUC) for the nomogram to predict the survival for 1, 3, and 5-year was 0.726, 0.816, and 0.823, respectively.ConclusionThis proposed nomogram shows the potential to make a precise prediction regarding the prognosis of HBV-related HCC patients and may help to stratify patients for personalized therapy following partial hepatectomy.

Dataset Information

Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy.

Publications

Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy.

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