scholarly journals Increased Expression of miR-487b Is Associated With Poor Prognosis and Tumor Progression of HBV-Related Hepatocellular Carcinoma

2020 ◽  
Vol 7 (12) ◽  
Author(s):  
Xiangang Cao ◽  
Qian Yang ◽  
Qing Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Hepatitis B ◽  
Roc Curve ◽  
Cox Regression ◽  
Migration And Invasion ◽  
Healthy Controls ◽  
Cox Regression Analysis ◽  
Specificity And Sensitivity ◽  
Tumor Node Metastasis Stage

Abstract Background Increasing evidence has demonstrated the involvement of microRNAs in the pathogenesis of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). The aims of this study were to analyze whether miR-487b can be used as a diagnostic and prognostic biomarker for HBV-related HCC and to explore its effect on the biological function of HCC. Methods The expression levels of miR-487b in the serum of all subjects were measured by real-time quantitative fluorescence polymerase chain reaction. The diagnostic value of miR-487b in serum was assessed using the receiver operating characteristic (ROC) curve. The relationship between miR-487b and the clinical data of patients was analyzed using the chi-square test. The prognostic value of miR-487b in HCC was assessed by Cox regression analysis and Kaplan-Meier survival. Moreover, CCK-8 and Transwell assays were performed to investigate the effect of miR-487b on HBV-related HCC function. Results Our data indicated that miR-487b in HCC patients was significantly higher than in chronic hepatitis B (CHB) patients and healthy controls. Meanwhile, the ROC curve showed that miR-487b had high specificity and sensitivity in the diagnosis of HBV-related HCC. MiR-487b can significantly distinguish between HCC patients and healthy controls and can differentiate HCC patients from CHB patients. Cox regression analysis showed that miR-487b was an independent risk factor. Overexpression of miR-487b was associated with Tumor Node Metastasis stage stage and Barcelona Clinic Liver Cancer stage in HCC patients. Cell function experiments demonstrated that upregulated miR-487b promoted cell proliferation, migration, and invasion. Conclusions Combined the results of the current study demonstrate that the upregulation of serum miR-487b may serve as a promising noninvasive diagnostic biomarker for HBV-related HCC.

A novel signature based on m6A related genes as the potential prognostic factor in hepatocellular carcinoma.

2020 ◽  
Author(s):  
Zhuomao Mo ◽  
Shaoju Luo ◽  
Hao Hu ◽  
Ling Yu ◽  
Zhirui Cao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Roc Curve ◽  
Cox Regression ◽  
Risk Group ◽  
Immune Therapy ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Potential Biomarker ◽  
Significant Difference

Abstract Background Many different signatures and models have been established for patients with hepatocellular carcinoma (HCC), but no signature based on m6A related genes was developed. The objective of this research was to establish the signature with m6A related genes in HCC. Methods Data from 377 HCC patients from The Cancer Genome Atlas (TCGA) database was downloaded. The included m6A related genes were selected by Cox regression analysis and the signature was verified by survival analysis and multiple receiver operating characteristic (ROC) curve. Furthermore, the nomogram was constructed and evaluated by C-index, calibration plot and ROC curve. Results The signature was established with the four m6A related genes (YTHDF2, YTHDF1, METTL3 and KIAA1429). Under the grouping from signature, patients in high risk group of showed the poor prognosis than those in low risk group. And significant difference was found in two kinds of immune cells (T cell gamma delta and NK cells activated) between two groups. The univariate and multivariate Cox regression analysis indicated that m6A related signature can be the potential independent prognosis factor in HCC. Finally, we developed a clinical risk model predicting the HCC prognosis and successfully verified it in C-index, calibration and ROC curve. Conclusion Our study identified the m6A related signature for predicting prognosis of HCC and provided the potential biomarker between m6A and immune therapy.

scholarly journals Effects of miRNA-140 on the Growth and Clinical Prognosis of SMMC-7721 Hepatocellular Carcinoma Cell Line

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Cun-qing Kong ◽  
Xing-cai Chen ◽  
Guan-hua Qiu ◽  
Jing-chen Liang ◽  
Duo Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Cox Regression ◽  
Expression Level ◽  
Migration And Invasion ◽  
Clinical Prognosis ◽  
Cox Regression Analysis ◽  
Qrt Pcr ◽  
Kaplan Meier ◽  
Hcc Cells

Background. A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested. Methods. The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan–Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140. Results. QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues ( P < 0.0001 ). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion ( P < 0.05 ), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion ( P < 0.05 ). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan–Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004 ) and overall survival (OS) times ( P = 0.010 ) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS ( P = 0.004 ) and OS times ( P = 0.014 ) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC.

scholarly journals Idenfication of a novel signature based on mTORC1 pathway for hepatocellular carcinoma.

2020 ◽  
Author(s):  
Zhuomao Mo ◽  
Shaoju Luo ◽  
Zhirui Cao ◽  
Hao Hu ◽  
Ling Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Roc Curve ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
Signal Pathway ◽  
Cancer Genome ◽  
Cox Regression Analysis

Abstract Background mTORC1 signal pathway play a role in the initiation and progression of hepatocellular carcinoma (HCC), but no relevant gene signature was developed. This research aimed to explore the potential correlation between mTORC1 signal pathway and HCC and establish the related genes signature. Methods HCC cases were retrieved from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. The genes to be included in mTORC1-assiociated signature were selected by performing univariate, multivariate Cox regression analysis and lasso regression analysis. Then, the signature was verified by survival analysis and multiple receiver operating characteristic (ROC) curve. Furthermore, a nomogram was established and evaluated by C-index, calibration plot and ROC curve. Results The signature was established with the six genes ( ETF1, GSR, SKAP2, HSPD1, CACYBP and PNP ). Under the grouping from signature, patients in the high- risk group showed worse survival than those in the low-risk group in both three datasets. The univariate and multivariate Cox regression analysis indicated that mTORC1 related signature can be the potential independent prognostic factor in HCC. Conclusion The mTORC1 associated gene signature established and validated in our research could be used as a potential prognostic factor in HCC.

scholarly journals Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Junbin Yan ◽  
Jielu Cao ◽  
Zhiyun Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Risk Score ◽  
Roc Curve ◽  
Prognostic Model ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Cox Analysis ◽  
Kaplan Meier Plotter

Abstract Background Apoptosis-related genes(Args)play an essential role in the occurrence and progression of hepatocellular carcinoma(HCC). However, few studies have focused on the prognostic significance of Args in HCC. In the study, we aim to explore an efficient prognostic model of Asian HCC patients based on the Args. Methods We downloaded mRNA expression profiles and corresponding clinical data of Asian HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The Args were collected from Deathbase, a database related to cell death, combined with the research results of GeneCards、National Center for Biotechnology Information (NCBI) databases and a lot of literature. We used Wilcoxon-test and univariate Cox analysis to screen the differential expressed genes (DEGs) and the prognostic related genes (PRGs) of HCC. The intersection genes of DEGs and PGGs were seen as crucial Args of HCC. The prognostic model of Asian HCC patients was constructed by least absolute shrinkage and selection operator (lasso)- proportional hazards model (Cox) regression analysis. Kaplan-Meier curve, Principal Component Analysis (PCA) analysis, t-distributed Stochastic Neighbor Embedding (t-SNE) analysis, risk score curve, receiver operating characteristic (ROC) curve, and the HCC data of ICGC database and the data of Asian HCC patients of Kaplan-Meier plotter database were used to verify the model. Results A total of 20 of 56 Args were differentially expressed between HCC and adjacent normal tissues (p < 0.05). Univariate Cox regression analysis showed that 10 of 56 Args were associated with survival time and survival status of HCC patients (p < 0.05). There are seven overlapping genes of these 20 and 10 genes, including BAK1, BAX, BNIP3, CRADD, CSE1L, FAS, and SH3GLB1. Through Lasso-Cox analysis, an HCC prognostic model composed of BAK1, BNIP3, CSE1L, and FAS was constructed. Kaplan-Meier curve, PCA, t-SNE analysis, risk score curve, ROC curve, and secondary verification of ICGC database and Kaplan-Meier plotter database all support the reliability of the model. Conclusions Lasso-Cox regression analysis identified a 4-gene prognostic model, which integrates clinical and gene expression and has a good effect. The expression of Args is related to the prognosis of HCC patients, but the specific mechanism remains to be further verified.

scholarly journals Clinical value evaluation of microRNA-324-3p and other available biomarkers in patients with HBV-infection-related hepatocellular carcinoma

2021 ◽  
Author(s):  
Li Zhao ◽  
Qian Yang ◽  
Jianbo Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatitis B ◽  
Diagnostic Performance ◽  
Cox Regression ◽  
Hbv Infection ◽  
Healthy Controls ◽  
Survival Prognosis ◽  
Diagnosis And Prognosis ◽  
Hcc Cells

Abstract Background Patients with hepatitis B virus (HBV) infection are at high risk of hepatocellular carcinoma (HCC). This study aimed to evaluate the expression of microRNA-324-3p (miR-324-3p) in HBV-related HCC, and explore the clinical significance of serum miR-324-3p and other available biomarkers in the diagnosis and prognosis of HBV-related HCC. Methods Expression of miR-324-3p in HBV-infection-related cells and patients was estimated using quantitative real-time PCR. The receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of serum miR-324-3p, AFP and PIVKA-II in the differentiation of HBV-related HCC from healthy controls and chronic hepatitis B (CHB). The relationship between serum miR-324-3p and patients’ clinical features was assessed using Chi-square test, and the value of miR-324-3p to predict overall survival prognosis was evaluated using Kaplan-Meier methods and Cox regression assay in patients with HBV-related HCC. Results HBV-related HCC cells had significantly increased miR-324-3p compared with normal and HBV-unrelated HCC cells, and serum miR-324-3p in HCC patients with HBV infection was also higher than that in healthy controls and CHB. Serum miR-324-3p had relatively high diagnostic accuracy for the screening of HCC case with HBV infection, and the combination of miR-324-3p, AFP and PIVKA-II showed the improved diagnostic performance. Additionally, high serum miR-324-2p in HBV-related HCC patients was associated with cirrhosis, tumor size, clinical stage and poor overall survival prognosis. Conclusion Serum increased miR-324-3p may be involved in the progression of HBV-related hepatitis to HCC, and may serve as a candidate biomarker for the diagnosis and prognosis of HBV-related HCC.

scholarly journals The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

2021 ◽  
Author(s):  
Philip J. Johnson ◽  
Sofi Dhanaraj ◽  
Sarah Berhane ◽  
Laura Bonnett ◽  
Yuk Ting Ma
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Prognostic Models ◽  
Controlled Study ◽  
Cox Regression Analysis ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Significant Difference

Abstract Background The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). Methods In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. Results On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. Conclusion NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.

scholarly journals The expression of miR-211-5p in atherosclerosis and its influence on diagnosis and prognosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanxia Zhang ◽  
Huiyun Wang ◽  
Yu Xia
Keyword(s):  
Roc Curve ◽  
Cox Regression ◽  
Survival Curve ◽  
Prognostic Significance ◽  
Significant Negative Correlation ◽  
Diagnostic Value ◽  
Expression Level ◽  
Healthy Controls ◽  
Cox Regression Analysis ◽  
Diagnosis And Prognosis

Abstract Background The purpose of this study was to evaluate the diagnostic and prognostic significance of miR-211-5p in atherosclerosis (AS) by detecting the expression level in serum of patients with AS. Methods A total of 85 healthy controls and 90 asymptomatic AS patients participated in this study. The expression level of miR-211-5p in all subjects were measured by qRT-PCR. Spearman correlation coefficient was used to evaluate the correlation of miR-211-5p with CRP and CIMT. The ROC curve was established to assess the diagnostic value of miR-211-5p in AS. The Kaplan–Meier survival curve and multivariate COX regression analysis were used to evaluate the prognostic significance of miR-211-5p in AS. Results The expression levels of miR-211-5p in AS patients were significantly lower than in healthy controls (P < 0.001), and miR-211-5p showed a significant negative correlation with CRP (r =  − 0.639, P < 0.001) and CIMT (r =  − 0.730, P < 0.001). The AUC of the ROC curve was 0.900, the specificity and the sensitivity were 84.7% and 78.9%, respectively, which indicating that miR-211-5p had diagnostic value for AS. Survival analysis showed that patients with low miR-211-5p expression were more likely to have cardiovascular end-point events (Log rank P = 0.013). Conclusion Serum miR-211-5p could be used as a new biomarker for the diagnosis of AS, and the low expression of miR-211-5p is associated with the poor prognosis of AS.

scholarly journals Identification of Immune-Related Prognostic mRNA and lncRNA in Patients with Hepatocellular Carcinoma

2022 ◽  
Vol 2022 ◽  
pp. 1-16
Author(s):  
Dan Chen ◽  
Xiaoting Li ◽  
Hui Li ◽  
Kai Wang ◽  
Xianghua Tian
Keyword(s):  
Hepatocellular Carcinoma ◽  
Flow Cytometry ◽  
T Cells ◽  
Regression Analysis ◽  
Survival Analysis ◽  
Immune Cells ◽  
Cox Regression ◽  
Differentially Expressed ◽  
Cox Regression Analysis ◽  
Immune Related Genes

Background. As the most common hepatic malignancy, hepatocellular carcinoma (HCC) has a high incidence; therefore, in this paper, the immune-related genes were sought as biomarkers in liver cancer. Methods. In this study, a differential expression analysis of lncRNA and mRNA in The Cancer Genome Atlas (TCGA) dataset between the HCC group and the normal control group was performed. Enrichment analysis was used to screen immune-related differentially expressed genes. Cox regression analysis and survival analysis were used to determine prognostic genes of HCC, whose expression was detected by molecular experiments. Finally, important immune cells were identified by immune cell infiltration and detected by flow cytometry. Results. Compared with the normal group, 1613 differentially expressed mRNAs (DEmRs) and 1237 differentially expressed lncRNAs (DElncRs) were found in HCC. Among them, 143 immune-related DEmRs and 39 immune-related DElncRs were screened out. These genes were mainly related to MAPK cascade, PI3K-AKT signaling pathway, and TGF-beta. Through Cox regression analysis and survival analysis, MMP9, SPP1, HAGLR, LINC02202, and RP11-598F7.3 were finally determined as the potential diagnostic biomarkers for HCC. The gene expression was verified by RT-qPCR and western blot. In addition, CD4 + memory resting T cells and CD8 + T cells were identified as protective factors for overall survival of HCC, and they were found highly expressed in HCC through flow cytometry. Conclusion. The study explored the dysregulation mechanism and potential biomarkers of immune-related genes and further identified the influence of immune cells on the prognosis of HCC, providing a theoretical basis for the prognosis prediction and immunotherapy in HCC patients.

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 Construction and Validation of a Metabolic Reprogramming Related Prognostic Model for Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Xiaohong - Liu ◽  
Qian - Xu ◽  
Zi-Jing - Li ◽  
Bin - Xiong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Risk Score ◽  
Prognostic Model ◽  
Cox Regression ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Metabolic Reprogramming ◽  
Cox Regression Analysis ◽  
Metabolic Genes

Abstract BackgroundMetabolic reprogramming is an important hallmark in the development of malignancies. Numerous metabolic genes have been demonstrated to participate in the progression of hepatocellular carcinoma (HCC). However, the prognostic significance of the metabolic genes in HCC remains elusive. MethodsWe downloaded the gene expression profiles and clinical information from the GEO, TCGA and ICGC databases. The differently expressed metabolic genes were identified by using Limma R package. Univariate Cox regression analysis and LASSO (Least absolute shrinkage and selection operator) Cox regression analysis were utilized to uncover the prognostic significance of metabolic genes. A metabolism-related prognostic model was constructed in TCGA cohort and validated in ICGC cohort. Furthermore, we constructed a nomogram to improve the accuracy of the prognostic model by using the multivariate Cox regression analysis.ResultsThe high-risk score predicted poor prognosis for HCC patients in the TCGA cohort, as confirmed in the ICGC cohort (P < 0.001). And in the multivariate Cox regression analysis, we observed that risk score could act as an independent prognostic factor for the TCGA cohort (HR (hazard ratio) 3.635, 95% CI (confidence interval)2.382-5.549) and the ICGC cohort (HR1.905, 95%CI 1.328-2.731). In addition, we constructed a nomogram for clinical use, which suggested a better prognostic model than risk score.ConclusionsOur study identified several metabolic genes with important prognostic value for HCC. These metabolic genes can influence the progression of HCC by regulating tumor biology and can also provide metabolic targets for the precise treatment of HCC.

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