Dopamine and dopamine receptor D1 as a novel favourable biomarker for 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.

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CYSTM1: A Novel Biomarker for Hepatocellular Carcinoma Prognosis

10.21203/rs.3.rs-150866/v1 ◽

2021 ◽

Author(s):

Jun Du ◽

Jinguo Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Early Stage ◽

Human Tumor ◽

The Cancer Genome Atlas ◽

Data Set ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Cox Proportional Hazard Regression ◽

The Relationship

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.

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Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

10.21203/rs.3.rs-471663/v1 ◽

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.

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Associations of Serum Tumor Biomarkers with Integrated Genomic and Clinical Characteristics of Hepatocellular Carcinoma

Liver Cancer ◽

10.1159/000516957 ◽

2021 ◽

pp. 1-13

Author(s):

Keun Soo Ahn ◽

Daniel R. O’Brien ◽

Yong Hoon Kim ◽

Tae-Seok Kim ◽

Hiroyuki Yamada ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Lens Culinaris ◽

Acid Metabolism ◽

The Cancer Genome Atlas ◽

Molecular Characteristics ◽

Genetic Profile ◽

Vegf Signaling ◽

The Usa ◽

Cancer Genome Atlas ◽

Liver Hepatocellular Carcinoma

Introduction: Serum α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) are useful biomarkers of hepatocellular carcinoma (HCC). However, associations among molecular characteristics and serum biomarkers are unclear. We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) to examine their associations with serum biomarker levels and clinical data. Methods: From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea and the USA and measured AFP, AFP-L3, and DCP from preoperatively obtained serum. We conducted an integrative clinical and molecular analysis, focusing on biomarkers, and validated the findings with the remaining 280 patients in the TCGA-LIHC cohort. Results: Patients were categorized into 4 subgroups: elevated AFP or AFP-L3 alone (↑AFP&L3), elevated DCP alone (↑DCP), elevation of all 3 biomarkers (elevated levels of all 3 biomarkers [↑All]), and reference range values for all biomarkers (RR). CTNNB1 variants were frequently observed in ↑DCP patients (53.8%) and RR patients (38.5%), but ↑DCP patients with a CTNNB1 variant had worse survival than RR patients. TP53 sequence variants were associated with ↑AFP (30.8%) and ↑DCP (30.8%). The Wnt-β-catenin signaling pathway was activated in the ↑AFP&L3, whereas liver-related Wnt signaling was activated in the RR. TGF-β and VEGF signaling were activated in ↑AFP&L3, whereas dysregulated bile acid and fatty acid metabolism were dominant in ↑DCP. We validated these findings by showing similar results between the test cohort and the remainder of the TCGA-LIHC cohort. Conclusions: Serum AFP, AFP-L3, and DCP levels can help predict variants in the genetic profile of HCC, especially for TP53 and CTNNB1. These findings may facilitate development of an evidence-based approach to treatment.

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Identification of RASSF1A Promoter Hypermethylation as a Biomarker for Hepatocellular Carcinoma

10.21203/rs.3.rs-54668/v2 ◽

2020 ◽

Author(s):

Gang Xu ◽

Xiaoxiang Zhou ◽

Jiali Xing ◽

Yao Xiao ◽

Bao Jin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Promoter Methylation ◽

Meta Analysis ◽

Promoter Hypermethylation ◽

Analysis Data ◽

Clinicopathological Characteristics ◽

The Cancer Genome Atlas ◽

Large Tumor ◽

Kaplan Meier ◽

Cancer Genome Atlas

Abstract Background: RAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial.Methods: We evaluated how RASSF1A promoter hypermethylation affects HCC risk and its clinicopathological characteristics through meta-analysis. Data on DNA methylation in HCC and relevant clinical data were also collected based on The Cancer Genome Atlas (TCGA) database to investigate the prognostic role of RASSF1A promoter hypermethylation in HCC.Results: Forty-four articles involving 4,777 individuals were enrolled in the pooled analyses. The RASSF1A promoter methylation rate was notably higher in the HCC cases than the non-tumor cases and healthy individuals, and was significantly related to hepatitis B virus (HBV) infection-positivity and large tumor size. Kaplan–Meier survival analysis revealed that HCC cases with RASSF1A promoter hypermethylation had worse outcomes. Receiver operating characteristic curves confirmed that RASSF1A promoter methylation may be a marker of HCC-related prognoses.Conclusions: RASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood, and is an emerging therapeutic target against HCC.

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Bioinformatics Analysis and Insights for The Role of COMMD7 in Hepatocellular Carcinoma

10.21203/rs.3.rs-79438/v1 ◽

2020 ◽

Author(s):

Xuehui Peng ◽

Yonggang He ◽

Xiaobing Huang ◽

Nan You ◽

Huiying Gu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bioinformatics Analysis ◽

Tissue Expression ◽

The Cancer Genome Atlas ◽

Research Progress ◽

Kaplan Meier ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Kaplan Meier Plotter

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions：This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.

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The m6A Methylation Gene SNRPC can be used as a Biomarker for the Prognosis and Immunotherapy of Hepatocellular Carcinoma

10.21203/rs.3.rs-320369/v1 ◽

2021 ◽

Author(s):

Jihao Cai ◽

Minglei Zhou ◽

Jianxin Xu

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Rna Methylation ◽

Kaplan Meier ◽

Pathogenic Factors ◽

Therapeutic Value ◽

Cancer Genome Atlas ◽

Checkpoint Inhibitor Therapy ◽

Genome Consortium

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Due to its complex pathogenic factors, the prognosis of HCC is poor. Therefore, a credible prognostic biomarker is urgently needed for this disease. N6-methyladenosine (m6A) RNA methylation plays an important role in the tumorigenesis, progression and prognosis of many tumors. However, studies on the prognostic and therapeutic value of this modification in HCC are lacking.Case Presentation: The HCC RNA-seq profiles in The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, including 421 LIHC and 440 LIRI samples respectively, were used in this study. The expressive distinction of 21 RNA methylation regulators between HCC and normal tissue were firstly assessed and SNRPC was obtained. Then the expression of SNRPC was validated as a risk factor for prognosis by Kaplan-Meier analysis and employed to establish a nomogram with T pathologic stage. By GSVA and GSEA analyses, we found SNRPC was mainly related to protein metabolism and immune process. Further, ESTIMATE, MCP-counter and single sample GSEA (ssGSEA) algorithm showed high-SNRPC expression group had lower stromal scores, a lower abundance of endothelial cells, fibroblasts and immune infiltration. Ultimately, Tumor Immune Dysfunction and Exclusion (TIDE) analysis exhibited high-SNRPC expression group showed non-response to immune checkpoint inhibitor therapy, especially to a PD-1 inhibitor.Conclusion: SNRPC could serve as valuable prognostic and immunotherapeutic marker in HCC. We provide here an accurate nomogram for clinical diagnosis using SNRPC as a biomarker.

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Caspase 4 Overexpression in Clear Cell Renal Cell Carcinoma and Its Prognostic Role

10.21203/rs.3.rs-35104/v1 ◽

2020 ◽

Author(s):

Lingfeng Meng ◽

Zijian Tian ◽

Xingbo Long ◽

Tongxiang Diao ◽

Maolin Hu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

The Cancer Genome Atlas ◽

Cell Renal Cell Carcinoma ◽

Normal Tissues ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Genome Atlas

Abstract Background: Caspase 4 (CASP4) dysregulation is related to the occurrence, development, and outcome of many malignant tumors, but its role in clear cell renal cell carcinoma (ccRCC) is unclear. This study was conducted to investigate the expression level of CASP4 in tumor tissues and its relationship with clinical prognosis of patients with ccRCC. Methods: First, the Oncomine and The Cancer Genome Atlas databases were used to determine CASP4 mRNA expression in ccRCC and its association with ccRCC prognosis. We then performed immunohistochemical staining and evaluation of 30 paired ccRCC and adjacent normal tissues to confirm these results. The correlation between CASP4 expression and ccRCC prognosis was evaluated using Kaplan-Meier analysis, and related genes and pathways were obtained from The Cancer Genome Atlas database by gene set enrichment analysis and gene set variation analysis. Finally, we explored the co-expression of genes with CASP4 in ccRCC. Results: CASP4 mRNA expression in ccRCC was significantly higher than that in normal tissues (p < 0.001). Kaplan-Meier analysis showed that the overall survival of patients with ccRCC showing high CASP4 expression was significantly reduced (p < 0.001). We then used external datasets (Gene Expression Omnibus database and patients from our center) to verify the level of CASP4 expression and survival differences (all p < 0.05). We also found that differential expression levels of CASP4 were correlated with pathological grade and clinical TNM stage (all p < 0.05). Conclusions: Overall, our study shows that CASP4 is highly expressed in ccRCC and is an important factor affecting prognosis. Thus, CASP4 may be a potential prognostic biomarker of ccRCC.

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

10.21203/rs.3.rs-725619/v1 ◽

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.

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From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma

PeerJ ◽

10.7717/peerj.3089 ◽

2017 ◽

Vol 5 ◽

pp. e3089 ◽

Cited By ~ 12

Author(s):

Hong Yang ◽

Xin Zhang ◽

Xiao-yong Cai ◽

Dong-yue Wen ◽

Zhi-hua Ye ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Big Data ◽

Natural Language Processing ◽

Language Processing ◽

Poor Prognosis ◽

Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Liver Hepatocellular Carcinoma ◽

Genome Atlas

BackgroundLiver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in.MethodsBig data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes. Relevant signaling pathways of differentially expressed genes went through Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes and Panther pathway enrichment analysis and protein-protein interaction network. The pathway ranked high in the enrichment analysis was further investigated, and selected genes with top priority were evaluated and assessed in terms of their diagnostic and prognostic values.ResultsA list of 389 genes was generated by overlapping genes from The Cancer Genome Atlas and Natural Language Processing. Three pathways demonstrated top priorities, and the one with specific associations with cancers, ‘pathways in cancer,’ was analyzed with its four highlighted genes, namely, BIRC5, E2F1, CCNE1, and CDKN2A, which were validated using Oncomine. The detection pool composed of the four genes presented satisfactory diagnostic power with an outstanding integrated AUC of 0.990 (95% CI [0.982–0.998],P < 0.001, sensitivity: 96.0%, specificity: 96.5%). BIRC5 (P = 0.021) and CCNE1 (P = 0.027) were associated with poor prognosis, while CDKN2A (P = 0.066) and E2F1 (P = 0.088) demonstrated no statistically significant differences.DiscussionThe study illustrates liver hepatocellular carcinoma gene signatures, related pathways and networks from the perspective of big data, featuring the cancer-specific pathway with priority, ‘pathways in cancer.’ The detection pool of the four highlighted genes, namely BIRC5, E2F1, CCNE1 and CDKN2A, should be further investigated given its high evidence level of diagnosis, whereas the prognostic powers of BIRC5 and CCNE1 are equally attractive and worthy of attention.

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ARRB2 promotes colorectal cancer growth through triggering WTAP

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa151 ◽

2020 ◽

Author(s):

Hongguang Liang ◽

Zelong Lin ◽

Youqiong Ye ◽

Rongcheng Luo ◽

Lixian Zeng

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Wilms Tumor ◽

The Cancer Genome Atlas ◽

Cancer Pathways ◽

Normal Tissues ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

And Migration ◽

Proliferation And Migration

Abstract Colorectal cancer (CRC) is one of the most lethal cancers worldwide. The expression of β-arrestin2 (β-Arr2, ARRB2) in CRC has been well investigated; however, its exact mechanism causing the cancer progression remains unclear. In this study, we discovered that the expression level of ARRB2 was significantly upregulated in CRC as compared to the normal tissues by employing the Cancer Genome Atlas (TCGA) data, western blot analysis, and immunohistochemistry. Furthermore, the level of ARRB2 was correlated with the patients’ overall survival by Kaplan–Meier analysis. The higher expression of ARRB2 promoted CRC cell growth, enhanced the cell motility, and blocked cell apoptosis, which is crucial for tumor growth. Lastly, the suppression of ARRB2 expression was enough to attenuate the progression of CRC induced by azoxymethane/dextran sodium sulfate. Interestingly, we also found that the knockdown of ARRB2 decreased several cancer pathways mediated by the expression of Wilms tumor 1 associated protein (WTAP), which led to the inhibition of cell proliferation and migration. Altogether, our results demonstrated that ARRB2 promoted the growth and migration of CRC cells by regulating the WTAP expression.

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