scholarly journals Identification of Prognostic Biomarkers and Independent Indicators Among PFDN1/2/3/4/5/6 in Liver Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Yin-Hai Dai ◽  
Fuping Li ◽  
Wei-Jie Kong ◽  
Xue-Qin Zhang ◽  
Mao Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Human Cancer ◽  
Normal Liver ◽  
The Cancer Genome Atlas ◽  
Prognostic Biomarkers ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Human Protein Atlas ◽  
Liver Hepatocellular Carcinoma

Abstract Background: Previous studies have proved that the aberrant expressions of PFDNs (Prefoldin) family proteins were correlated with several human cancer. However, the specific functions of PFDNs in liver hepatocellular carcinoma(LIHC) remain unknown. The study aimed to identify the prognostic biomarkers and independent indicators among PFDN1/2/3/4/5/6 in liver hepatocellular carcinoma.Methods: We used these databases including Oncomine, Ualcan, GEPIA2, Human Protein Atlas, The Cancer Genome Atlas, Kaplan-Meier plotter, cBioPortal, STRI-NG and TIMER and the software of Cytoscape in our study.Results: PFDN1/2/3/4/5/6 were highly expressed in LIHC tissues. The mRNA expression levels of PFDN1/2/3/4/5/6 were relevant to tumor grades.PFDN1/3/4/5 expressions significantly changed in different cancer stages. The protein expression levels of PFDNs were higher in LIHC tissue than normal liver tissue. Moreover, High mRNA expressions of PFDN1/2/3/4 were associated with shorter OS of LIHC patients. In multivariate analysis,high expressions of PFDN1/2/4 were independently correlated with poorer OS of LIHC patients. In our findings,55% of patients with LIHC had genetic mutations on PFDNs. Besides, there were significant associations between the expressions of PFDN1/2/3/4/5 and six types of infiltrated immune cells(B cells, CD4+T cells, CD8+T cells, neutrophil, macrophage, and dendritic cells).Conclusions:PFDN1/2/3/4 were potential prognostic markers to suggest poor OS of LIHC patients. In addition, high PFDN1/2/4 expressions were independent prognostic factors in OS for LIHC patients.

scholarly journals Expression and clinical significance of miR-3615 in hepatocellular carcinoma

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Curve ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Prognostic Information ◽  
Ki 67 ◽  
Tissue Samples ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Serum Alpha Fetoprotein

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.

scholarly journals Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Chi Square ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Liver Hepatocellular Carcinoma ◽  
The Relationship

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.

scholarly journals Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma

2021 ◽  
Vol 17 (1) ◽  
pp. 142-151
Author(s):  
Jingqi Liu ◽  
Ligang Chen ◽  
Jinshui Pan ◽  
Meiya Chen ◽  
Jingping Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Expression Levels ◽  
Go Analysis ◽  
The Public ◽  
Kaplan Meier ◽  
Tcga Dataset ◽  
Underlying Mechanisms

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.Material and methodsOur study represented the comprehensive analysis of differentially expressed lncRNAs in HCV-positive HCC for the first time by analyzing the public dataset GSE17856. Co-expression network and gene ontology (GO) analysis revealed the functions of those differentially expressed lncRNAs.ResultsWe identified 256 upregulated lncRNAs and 198 downregulated lncRNAs in HCV- positive HCC compared to the normal liver tissues. Co-expression network and GO analysis showed that these lncRNAs were involved in regulating metabolism, energy pathways, proliferation and the immune response. Seven lncRNAs (LOC341056, CCT6P1, PTTG3P, LOC643387, LOC100133920, C3P1 and C22orf45) were identified as key lncRNAs and co-expressed with more than 100 differentially expressed genes (DEGs) in HCV-related HCC. Kaplan-Meier analysis showed that higher expression levels of LOC643387, PTTG3P, LOC341056, CCT6P1 and lower expression levels of C3P1 and C22orf45 were associated with shorter survival time in the TCGA dataset.ConclusionsWe believe that this study can provide novel potential therapeutic and prognostic biomarkers for HCV-positive HCC.

scholarly journals Thymosin β 10 is overexpressed and associated with unfavorable prognosis in hepatocellular carcinoma

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Chunrong Song ◽  
Zhong Su ◽  
Jing Guo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Human Cancer ◽  
Normal Liver ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Tumor Biomarker ◽  
Advanced Tumor Stage ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Advanced Tumor

Abstract Thymosin β 10 (TMSB10) has been demonstrated to be overexpressed and function as an oncogene in most types of human cancer including hepatocellular carcinoma (HCC). In our study, we present more evidence about the clinical significance and biological function of TMSB10 in HCC. First, we observed levels of TMSB10 expression were obviously increased in HCC tissues compared with normal liver tissues at The Cancer Genome Atlas (TCGA) datasets. Furthermore, we confirmed that TMSB10 mRNA and protein levels were also increased in HCC tissue samples compared with normal adjacent normal liver tissue samples. In addition, we found high TMSB10 expression was remarkably associated with the advanced tumor stage, large tumor size, distant metastasis, and poor prognosis, and acted as an independent factor for predicting poor overall survival in HCC patients. Loss-of-function studies suggested silencing of TMSB10 expression dramatically reduced cell proliferation, migration, and invasion in HCC. In conclusion, TMSB10 may hold promise as a tumor biomarker for predicting prognosis and a potential target for developing a novel therapeutic strategy.

scholarly journals Prognostic Value of Phosphotyrosine Phosphatases in Hepatocellular Carcinoma

2018 ◽  
Vol 46 (6) ◽  
pp. 2335-2346 ◽  
Author(s):  
Guangyan Zhangyuan ◽  
Yin Yin ◽  
Wenjie Zhang ◽  
WeiWei Yu ◽  
Kangpeng Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
The Cancer Genome Atlas ◽  
Expression Levels ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Phosphotyrosine Phosphatases

Background/Aims: During the occurrence and progression of hepatocellular carcinoma (HCC), phosphotyrosine phosphatases (PTPs) are usually described as tumor suppressors or proto-oncogenes, and to some degree are correlated with the prognosis of HCC. Methods: A total of 321 patients from the Cancer Genome Atlas (TCGA) database and 180 patients from our validated cohort with hepatocellular carcinoma were recruited in this study. Kaplan-Meier, univariate and multivariate Cox proportional hazards model were used to evaluate the risk factors for survival. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were applied to detect the expression levels of PTP genes. Results: After screening the data of TCGA, we identified five PTPs as HCC overall survival related PTP genes, among which only three (PTPN12, PTPRN, PTPN18) exhibited differential expression levels in our 180 paired HCC and adjacent tissues (P< 0.001). Further analysis revealed that expression of PTPN18 was positively, but PTPRN was negatively associated with prognosis of HCC both in TCGA cohort and our own cohort. As to PTPN12, results turned out to be opposite according to HBV status. In detail, higher expression of PTPN12 was associated with better outcome in HBV group but worse prognosis in Non-HBV group. Conclusion: Our results suggested that PTPN12, PTPRN and PTPN18 were independent prognostic factors in HCC.

scholarly journals Comprehensive Characterization of Immunological Profiles and Clinical Significance in Hepatocellular Carcinoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Ping Tao ◽  
Liang Hong ◽  
Wenqing Tang ◽  
Qun Lu ◽  
Yanrong Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Nk Cells ◽  
Clinical Outcomes ◽  
Clinical Significance ◽  
Multivariate Regression Analysis ◽  
The Cancer Genome Atlas ◽  
Systematic Analysis ◽  
Kaplan Meier ◽  
Analysis System

BackgroundTherapies targeting immune molecules have rapidly been adopted and advanced the treatment of hepatocellular carcinoma (HCC). Nonetheless, no studies have reported a systematic analysis between immunological profiles and clinical significance in HCC.MethodsWe comprehensively investigated immune patterns and systematically correlated 22 types of both adaptive and innate immune cells with genomic characteristics and clinical outcomes based on 370 HCC patients from The Cancer Genome Atlas (TCGA) database through a metagene approach (known as CIBERSORT). Based on the Quantitative Pathology Imaging and Analysis System coupled with integrated high-dimensional bioinformatics analysis, we further independently validated six immune subsets (CD4+ T cells, CD8+ T cells, CD20+ B cells, CD14+ monocytes, CD56+ NK cells, and CD68+ macrophages), and shortlisted three (CD4+ T cells, CD8+ T cells, and CD56+ NK cells) of which to investigate their association with clinical outcomes in two independent Zhongshan cohorts of HCC patients (n = 258 and n = 178). Patient prognosis was further evaluated by Kaplan-Meier analysis and univariate and multivariate regression analysis.ResultsBy using the CIBERSORT method, the immunome landscape of HCC was constructed based on integrated transcriptomics analysis and multiplexed sequential immunohistochemistry. Further, the patients were categorized into four immune subgroups featured with distinct clinical outcomes. Strikingly, significant inter-tumoral and intra-tumoral immune heterogeneity was further identified according to the in-depth interrogation of the immune landscape.ConclusionThis work represents a potential useful resource for the immunoscore establishment for prognostic prediction in HCC patients.

scholarly journals The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12123
Author(s):  
Bi Peng ◽  
Yuanliang Yan ◽  
Zhijie Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Metal Ion ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Expression Levels ◽  
Normal Tissues ◽  
Molecular Profiles

Background Serving as N6-methyladenosine demethylases, the AlkB family is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the molecular profiles and clinical values of the AlkB family in HCC are not well known. Methods Several bioinformatics tools and in vitro experiments were used to identify the immune-related profiles and prognostic values of AlkB family in HCC. Results In this study expression levels of ALKBH1/2/3/4/7 were all remarkably increased in HCC tissues when compared with normal tissues. Quantitative PCR (qPCR) and immunohistochemistry were used to validate the expression of AlkB family members in HCC tissues and normal liver tissues. In addition, high expression levels of ALKBH4 were negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients with HCC. Increased ALKBH4 was also associated with pathological stage in HCC patients. The molecular profiles of AlkB family in HCC were mainly associated with peptidyl-serine modification, peptidyl-tyrosine modification, regulation of metal ion transport, etc. Furthermore, tumor-infiltrating immune cell analysis indicated that ALKBH1/2/3/4/5/6/7/8 and FTO were related to the infiltration of different immune cell, such as CD8+ T cells, macrophages, neutrophils, dendritic cells and CD4+ T cells. We also discovered that the methylation levels of ALKBH1/2/4/5/6/8 and FTO were remarkably reduced in HCC tissues. Conclusions Collectively, our findings may deepen the understanding of specific molecular profiles of the AlkB family in HCC pathology. In particular, ALKBH4 could serve as a promising prognostic candidate for treating HCC, and these results might potentiate the development of more reliable therapeutic strategies for patients with HCC.

scholarly journals Identification of Therapeutic Targets and Prognostic Biomarkers Among Chemokine (C-C Motif) Ligands in the Liver Hepatocellular Carcinoma Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhongyi Jiang ◽  
Changchang Xing ◽  
Pusen Wang ◽  
Xueni Liu ◽  
Lin Zhong
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Western Blot ◽  
Signaling Pathway ◽  
Immune Cells ◽  
Stromal Cells ◽  
Prognostic Biomarkers ◽  
Immune Checkpoints ◽  
Immunological Therapy ◽  
Liver Hepatocellular Carcinoma

Background: Liver hepatocellular carcinoma (LIHC) is the third leading cause of cancer-related death and the sixth most common solid tumor worldwide. In the tumor microenvironment, the cross-talk between cancer cells, immune cells, and stromal cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. Chemokine (C-C motif) ligands (CCL) can directly target tumor cells and stromal cells, and they have been shown to regulate tumor cell proliferation, cancer stem-like cell properties, cancer invasiveness and metastasis, which directly and indirectly affect tumor immunity and influence cancer progression, therapy and patient outcomes. However, the prognostic values of chemokines CCL in LIHC have not been clarified.Methods: In this study, we comprehensively analyzed the relationship between transcriptional chemokines CCL and disease progression of LIHC using the ONCOMINE dataset, GEPIA, UALCAN, STRING, WebGestalt, GeneMANIA, TRRUST, DAVID 6.8, LinkedOmics, TIMER, GSCALite, and Open Targets. We validated the protein levels of chemokines CCL through western blot and immunohistochemistry.Results: The transcriptional levels of CCL5/8/11/13/15/18/20/21/25/26/27/28 in LIHC tissues were significantly elevated while CCL2/3/4/14/23/24 were significantly reduced. A significant correlation was found between the expression of CCL14/25 and the pathological stage of LIHC patients. LIHC patients with low transcriptional levels of CCL14/21 were associated with a significantly poor prognosis. The functions of differentially expressed chemokines CCL were primarily related to the chemokine signaling pathway, cytokine–cytokine receptor interactions, and TNF-α signaling pathway. Our data suggested that RELA/REL, NFKB1, STAT1/3/6, IRF3, SPI1, and JUN were key transcription factors for chemokines CCL. We found significant correlations among the expression of chemokines CCL and the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) and immune checkpoints (PD-1. PD-L1, and CTLA-4). The western blot and immunohistochemistry results showed that protein expression levels of CCL5 and CCL20 were upregulated in LIHC. CCL5 and CCL20 were significantly correlated with the clinical outcome of patients with LIHC, and could be negatively regulated by some drugs or small molecules.Conclusions: Our results may provide novel insights for the potential suitable targets of immunological therapy and prognostic biomarkers for LIHC.

scholarly journals Dopamine and dopamine receptor D1 as a novel favourable biomarker for hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhihui Wang ◽  
Peihao Wen ◽  
Bowen Hu ◽  
Shengli Cao ◽  
Xiaoyi Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dopamine Receptor ◽  
Systematic Investigation ◽  
The Cancer Genome Atlas ◽  
Malignant Tumours ◽  
Functional Activities ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Liver Hepatocellular Carcinoma

Abstract Background Hepatocellular carcinoma (HCC) remains one of the most common malignant tumours worldwide. Therefore, the identification and development of sensitivity- genes as novel diagnostic markers and effective therapeutic targets is urgently needed. Dopamine and dopamine receptor D1 (DRD1) are reported to be involved in the progression of various cancers. However, the crucial role of DRD1 in HCC malignant activities remains unclear. Methods We enrolled 371 patients with liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) to detect the expression and functions of DRD1. The Tumour Immune Estimation Resource (TIMER), UALCAN database, Kaplan–Meier plotter, cBioPortal database, and LinkedOmics database were utilized for the systematic investigation of DRD1 expression and related clinical features, coexpressed genes, functional pathways, mutations, and immune infiltrates in HCC. Results In this study, we determined that DRD1 expression was decreased in HCC tumour tissues versus normal tissues and that low DRD1 expression indicated a poor prognosis. The significance of DRD1 expression varied among different tumour samples. The somatic mutation frequency of DRD1 in the LIHC cohort was 0.3%. The biological functions of DRD1 were detected and validated, and DRD1 was shown to be involved in various functional activities, including metabolism, oxidation, mitochondrial matrix-related processes and other related signaling pathways. In addition, out study indicated that DRD1 had significant correlations with the infiltration of macrophages, B cells and CD+ T cells in HCC. Conclusions These findings demonstrated the rationality of the potential application of DRD1 function as a novel biomarker for HCC diagnosis and a therapeutic target for HCC treatment.

scholarly journals Comprehensive Analysis of Aldehyde Dehydrogenases (ALDHs) and Its Significant Role in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Senbang Yao ◽  
Wenjun Chen ◽  
He Zuo ◽  
Ziran Bi ◽  
Xiuqing Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Oxidative Dna Damage ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Kaplan Meier ◽  
Human Protein Atlas ◽  
Cancer Genome Atlas ◽  
The Relationship ◽  
Kaplan Meier Plotter

AbstractOxidative DNA damage is closely related to the occurrence and progression of cancer. Oxidative stress plays an important role in alcohol-induced hepatocellular carcinoma (HCC). Aldehyde dehydrogenase (ALDH) is a family of enzymes that plays an essential role in the reducing oxidative damage. However, how ALDHs family affects alcohol-related HCC remains obscure. We aimed to explore the correlation between the differential expression of ALDHs in patients with HCC and pathological features, as well as the relationship between ALDHs and prognosis, and finally analyze the possible mechanism of ALDHs in targeted therapy of HCC. The data of HCC were downloaded from The Cancer Genome Atlas (TCGA) database. This research explored the expression and prognostic values of ALDHs in HCC using Oncomine, UALCAN, Human Protein Atlas, cBioPortal, Kaplan–Meier plotter, GeneMANIA, Tumor Immune Estimation Resource, GEPIA databases, and WebGestalt. Low mRNA and protein expressions of ALDHs were found to be significantly associated with tumor grade and clinical cancer stages in HCC patients. In particular, the loss of ALDH expression is more obvious in Asians, and its effect on prognosis is far more significant than that in the White race. Our findings play an important role in the study of prognostic markers and anti-liver cancer therapeutic targets for the members of the ALDHs family, especially in patients with liver cancer in Asia.

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