scholarly journals A novel five‐gene signature predicts overall survival of patients with hepatocellular carcinoma

2021 ◽  
Author(s):  
Zhigang Wang ◽  
Leyu Pan ◽  
Deliang Guo ◽  
Xiaofeng Luo ◽  
Jie Tang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Gene Signature

scholarly journals Identification of a five-gene signature in association with overall survival for hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11273
Author(s):  
Lei Yang ◽  
Weilong Yin ◽  
Xuechen Liu ◽  
Fangcun Li ◽  
Li Ma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Overall Survival ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Enrichment Score ◽  
Hub Genes ◽  
Cox Regression Analysis

Background Hepatocellular carcinoma (HCC) is considered to be a malignant tumor with a high incidence and a high mortality. Accurate prognostic models are urgently needed. The present study was aimed at screening the critical genes for prognosis of HCC. Methods The GSE25097, GSE14520, GSE36376 and GSE76427 datasets were obtained from Gene Expression Omnibus (GEO). We used GEO2R to screen differentially expressed genes (DEGs). A protein-protein interaction network of the DEGs was constructed by Cytoscape in order to find hub genes by module analysis. The Metascape was performed to discover biological functions and pathway enrichment of DEGs. MCODE components were calculated to construct a module complex of DEGs. Then, gene set enrichment analysis (GSEA) was used for gene enrichment analysis. ONCOMINE was employed to assess the mRNA expression levels of key genes in HCC, and the survival analysis was conducted using the array from The Cancer Genome Atlas (TCGA) of HCC. Then, the LASSO Cox regression model was performed to establish and identify the prognostic gene signature. We validated the prognostic value of the gene signature in the TCGA cohort. Results We screened out 10 hub genes which were all up-regulated in HCC tissue. They mainly enrich in mitotic cell cycle process. The GSEA results showed that these data sets had good enrichment score and significance in the cell cycle pathway. Each candidate gene may be an indicator of prognostic factors in the development of HCC. However, hub genes expression was weekly associated with overall survival in HCC patients. LASSO Cox regression analysis validated a five-gene signature (including CDC20, CCNB2, NCAPG, ASPM and NUSAP1). These results suggest that five-gene signature model may provide clues for clinical prognostic biomarker of HCC.

scholarly journals Identification of a Liver Progenitor Cell-Related Genes Signature Predicting Overall Survival for Hepatocellular Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110414
Author(s):  
Xiaoyong Li ◽  
Jiaqong Lin ◽  
Yuguo pan ◽  
Peng Cui ◽  
Jintang Xia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Regression Analysis ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
Regression Analyses ◽  
Related Gene ◽  
Cox Regression Analysis

Background: Liver progenitor cells (LPCs) play significant roles in the development and progression of hepatocellular carcinoma (HCC). However, no studies on the value of LPC-related genes for evaluating HCC prognosis exist. We developed a gene signature of LPC-related genes for prognostication in HCC. Methods: To identify LPC-related genes, we analyzed mRNA expression arrays from a dataset (GSE57812 & GSE 37071) containing LPCs, mature hepatocytes, and embryonic stem cell samples. HCC RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to explore the differentially expressed genes (DEGs) related to prognosis through DEG analysis and univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed to construct the LPC-related gene prognostic model in the TCGA training dataset. This model was validated in the TCGA testing set and an external dataset (International Cancer Genome Consortium [ICGC] dataset). Finally, we investigated the relationship between this prognostic model with tumor-node-metastasis stage, tumor grade, and vascular invasion of HCC. Results: Overall, 1770 genes were identified as LPC-related genes, of which 92 genes were identified as DEGs in HCC tissues compared with normal tissues. Furthermore, we randomly assigned patients from the TCGA dataset to the training and testing cohorts. Twenty-six DEGs correlated with overall survival (OS) in the univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed in the TCGA training set, and a 3-gene signature was constructed to stratify patients into 2 risk groups: high-risk and low-risk. Patients in the high-risk group had significantly lower OS than those in the low-risk group. Receiver operating characteristic curve analysis confirmed the signature's predictive capacity. Moreover, the risk score was confirmed to be an independent predictor for patients with HCC. Conclusion: We demonstrated that the LPC-related gene signature can be used for prognostication in HCC. Thus, targeting LPCs may serve as a therapeutic alternative for HCC.

scholarly journals Establishment and Validation of an MTORC1 Signaling-Related Gene Signature to Predict Overall Survival in Patients with Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Zheng Yao ◽  
Song Wen ◽  
Jun Luo ◽  
Weiyuan Hao ◽  
Weiren Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Decision Tree ◽  
Survival Data ◽  
Cox Regression ◽  
Gene Signature ◽  
Related Gene ◽  
Cox Regression Analysis ◽  
Cancer Hallmarks ◽  
Mtorc1 Signaling

Background. Accurate and effective biomarkers for the prognosis of patients with hepatocellular carcinoma (HCC) are poorly identified. A network-based gene signature may serve as a valuable biomarker to improve the accuracy of risk discrimination in patients. Methods. The expression levels of cancer hallmarks were determined by Cox regression analysis. Various bioinformatic methods, such as GSEA, WGCNA, and LASSO, and statistical approaches were applied to generate an MTORC1 signaling-related gene signature (MSRS). Moreover, a decision tree and nomogram were constructed to aid in the quantification of risk levels for each HCC patient. Results. Active MTORC1 signaling was found to be the most vital predictor of overall survival in HCC patients in the training cohort. MSRS was established and proved to hold the capacity to stratify HCC patients with poor outcomes in two validated datasets. Analysis of the patient MSRS levels and patient survival data suggested that the MSRS can be a valuable risk factor in two validated datasets and the integrated cohort. Finally, we constructed a decision tree which allowed to distinguish subclasses of patients at high risk and a nomogram which could accurately predict the survival of individuals. Conclusions. The present study may contribute to the improvement of current prognostic systems for patients with HCC.

scholarly journals Development of a Predictive Immune-Related Gene Signature Associated With Hepatocellular Carcinoma Patient Prognosis

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482097711
Author(s):  
Jiasheng Lei ◽  
Dengyong Zhang ◽  
Chao Yao ◽  
Sheng Ding ◽  
Zheng Lu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Cox Regression ◽  
R Package ◽  
Gene Signature ◽  
Differentially Expressed ◽  
Related Gene ◽  
Patient Cohort ◽  
Immune Related Gene ◽  
Related Risk

Background: Hepatocellular carcinoma (HCC) remains the third leader cancer-associated cause of death globally, but the etiological basis for this complex disease remains poorly clarified. The present study was thus conceptualized to define a prognostic immune-related gene (IRG) signature capable of predicting immunotherapy responsiveness and overall survival (OS) in patients with HCC. Methods: Five differentially expressed IRG associated with HCC were established the immune-related risk model through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Patients were separated at random into training and testing cohorts, after which the association between the identified IRG signature and OS was evaluated using the “survival” R package. In addition, maftools was leveraged to assess mutational data, with tumor mutation burden (TMB) scores being calculated as follows: (total mutations/total bases) × 106. Immune-related risk term abundance was quantified via “ssGSEA” algorithm using the “gsva” R package. Results: HCC patients were successfully stratified into low-risk and high-risk groups based upon a signature composed of 5 differentially expressed IRGs, with overall survival being significantly different between these 2 groups in training cohort, testing cohort and overall patient cohort ( P = 1.745e-06, P = 1.888e-02, P = 4.281e-07). No association was observed between TMB and this IRG risk score in the overall patient cohort ( P = 0.461). Notably, 19 out of 29 immune-related risk terms differed substantially in the overall patient dataset. These risk terms mainly included checkpoints, human leukocyte antigens, natural killer cells, dendritic cells, and major histocompatibility complex class I. Conclusion: In summary, an immune-related prognostic gene signature was successfully developed and used to predict survival outcomes and immune system status in patients with HCC. This signature has the potential to help guide immunotherapeutic treatment planning for patients affected by this deadly cancer.

scholarly journals A Nomogram Based on a Three-Gene Signature Derived from AATF Coexpressed Genes Predicts Overall Survival of Hepatocellular Carcinoma Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Jun Liu ◽  
Jianjun Lu ◽  
Zhanzhong Ma ◽  
Wenli Li
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Clinical Practice ◽  
Correlation Coefficient ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Signature ◽  
Cancer Genome ◽  
Survival Prediction

Background. Hepatocellular carcinoma (HCC) is a common cancer with an extremely high mortality rate. Therefore, there is an urgent need in screening key biomarkers of HCC to predict the prognosis and develop more individual treatments. Recently, AATF is reported to be an important factor contributing to HCC. Methods. We aimed to establish a gene signature to predict overall survival of HCC patients. Firstly, we examined the expression level of AATF in the Gene Expression Omnibus (GEO), the Cancer Genome Atlas (TCGA), and the International Union of Cancer Genome (ICGC) databases. Genes coexpressed with AATF were identified in the TCGA dataset by the Poisson correlation coefficient and used to establish a gene signature for survival prediction. The prognostic significance of this gene signature was then validated in the ICGC dataset and used to build a combined prognostic model for clinical practice. Results. Gene expression data and clinical information of 2521 HCC patients were downloaded from three public databases. AATF expression in HCC tissue was higher than that in matched normal liver tissues. 644 genes coexpressed with AATF were identified by the Poisson correlation coefficient and used to establish a three-gene signature (KIF20A, UCK2, and SLC41A3) by the univariate and multivariate least absolute shrinkage and selection operator Cox regression analyses. This three-gene signature was then used to build a combined nomogram for clinical practice. Conclusion. This integrated nomogram based on the three-gene signature can predict overall survival for HCC patients well. The three-gene signature may be a potential therapeutic target in HCC.

scholarly journals The Landscape of Glycosyltransferase Gene Signature for Overall Survival Prediction in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Qiang Cai ◽  
Shizhe Yu ◽  
Jian Zhao ◽  
Duo Ma ◽  
Long Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Risk Score ◽  
Prognostic Value ◽  
Cox Regression ◽  
Risk Groups ◽  
Gene Signature ◽  
Low Risk ◽  
Regression Analyses ◽  
Risk Patients

Abstract Background: Hepatocellular carcinoma (HCC) is heterogeneous disease occurring in the background of chronic liver diseases. The role of glycosyltransferase (GT) genes have recently been the focus of research associating with the development of tumors. However, the prognostic value of GT genes in HCC remains not elucidated. This study aimed to demonstrate the GT genes related to the prognosis of HCC through bioinformatics analysis.Methods: The GT genes signatures were identified from the training set of The Cancer Genome Atlas (TCGA) dataset using univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Then, we analyzed the prognostic value of GT genes signatures related to the overall survival (OS) of HCC patients. A prognostic model was constructed, and the risk score of each patient was calculated as formula, which divided HCC patients into high- and low-risk groups. Kaplan-Meier (K-M) and Receiver operating characteristic (ROC) curves were used to assess the OS of HCC patients. The prognostic value of GT genes signatures was further investigated in the validation set of TCGA database. Univariate and multivariate Cox regression analyses were performed to demonstrate the independent factors on OS. Finally, we utilized the gene set enrichment analysis (GSEA) to annotate the function of these genes between the two risk categories. Results: In this study, we identified and validated 4 GT genes as the prognostic signatures. The K-M analysis showed that the survival rate of the high-risk patients was significantly lower than that of the low-risk patients. The risk score calculated with 4 gene signatures could predict OS for 3-, 5-, and 7-year in patients with HCC, revealing the prognostic ability of these gene signature. In addition, Multivariate Cox regression analyses indicated that the risk score was an independent prognostic factor for HCC. Functional analysis further revealed that immune-related pathways were enriched, and immune status in HCC were different between the two risk groups.Conclusion: In conclusion, a novel GT genes signature can be used for prognostic prediction in HCC. Thus, targeting GT genes may be a therapeutic alternative for HCC.

scholarly journals Identification of a Pyroptosis-Related Gene Signature for Predicting Overall Survival and Response to Immunotherapy in Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Susu Zheng ◽  
Xiaoying Xie ◽  
Xinkun Guo ◽  
Yanfang Wu ◽  
Guobin Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Regression Model ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Related Gene

Pyroptosis is a novel kind of cellular necrosis and shown to be involved in cancer progression. However, the diverse expression, prognosis and associations with immune status of pyroptosis-related genes in Hepatocellular carcinoma (HCC) have yet to be analyzed. Herein, the expression profiles and corresponding clinical characteristics of HCC samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then a pyroptosis-related gene signature was built by applying the least absolute shrinkage and selection operator (LASSO) Cox regression model from the TCGA cohort, while the GEO datasets were applied for verification. Twenty-four pyroptosis-related genes were found to be differentially expressed between HCC and normal samples. A five pyroptosis-related gene signature (GSDME, CASP8, SCAF11, NOD2, CASP6) was constructed according to LASSO Cox regression model. Patients in the low-risk group had better survival rates than those in the high-risk group. The risk score was proved to be an independent prognostic factor for overall survival (OS). The risk score correlated with immune infiltrations and immunotherapy responses. GSEA indicated that endocytosis, ubiquitin mediated proteolysis and regulation of autophagy were enriched in the high-risk group, while drug metabolism cytochrome P450 and tryptophan metabolism were enriched in the low-risk group. In conclusion, our pyroptosis-related gene signature can be used for survival prediction and may also predict the response of immunotherapy.

scholarly journals A Seven-Gene Signature to Predict Prognosis of Patients With Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Junli Wang ◽  
Qi Zhang ◽  
Fukang Shi ◽  
Dipesh Kumar Yadav ◽  
Zhengtao Hong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Risk Group ◽  
Radical Resection ◽  
Tissue Microarrays ◽  
Gene Signature ◽  
High Risk Group ◽  
Prognostic Models ◽  
Risk Scores

Purpose: Hepatocellular carcinoma (HCC) is one of the most prevalent malignant diseases worldwide and has a poor prognosis. Gene-based prognostic models have been reported to predict the overall survival of patients with HCC. Unfortunately, most of the genes used in earlier prognostic models lack prospective validation and, thus, cannot be used in clinical practice.Methods: Candidate genes were selected from GEPIA (Gene Expression Profiling Interactive Analysis), and their associations with patients’ survival were confirmed by RT-PCR using cDNA tissue microarrays established from patients with HCC after radical resection. A multivariate Cox proportion model was used to calculate the coefficient of corresponding gene. The expression of seven genes of interest (MKI67, AR, PLG, DNASE1L3, PTTG1, PPP1R1A, and TTR) with two reference genes was defined to calculate a risk score which determined groups of different risks.Results: Our risk scoring efficiently classified patients (n = 129) with HCC into a low-, intermediate-, and high-risk group. The three groups showed meaningful distinction of 3-year overall survival rate, i.e., 88.9, 74.5, and 20.6% for the low-, intermediate-, and high-risk group, respectively. The prognostic prediction model of risk scores was subsequently verified using an independent prospective cohort (n = 77) and showed high accuracy.Conclusion: Our seven-gene signature model performed excellent long-term prediction power and provided crucially guiding therapy for patients who are not a candidate for surgery.

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