scholarly journals Identification and Validation of Key Genes in Hepatocellular Carcinoma by Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jia Wang ◽  
Rui Peng ◽  
Zheng Zhang ◽  
Yixi Zhang ◽  
Yuke Dai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Primary Liver Cancer ◽  
Interaction Network ◽  
Chemical Carcinogenesis ◽  
Parameter Analysis ◽  
Qrt Pcr ◽  
Key Genes

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and has poor outcomes. However, the potential molecular biological process underpinning the occurrence and development of HCC is still largely unknown. The purpose of this study was to identify the core genes related to HCC and explore their potential molecular events using bioinformatics methods. HCC-related expression profiles GSE25097 and GSE84005 were selected from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) between 306 HCC tissues and 281 corresponding noncancerous tissues were identified using GEO2R online tools. The protein-protein interaction network (PPIN) was constructed and visualized using the STRING database. Gene Ontology (GO) and KEGG pathway enrichment analyses of the DEGs were carried out using DAVID 6.8 and KOBAS 3.0. Additionally, module analysis and centrality parameter analysis were performed by Cytoscape. The expression differences of key genes in normal hepatocyte cells and HCC cells were verified by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). Additionally, survival analysis of key genes was performed by GEPIA. Our results showed that a total of 291 DEGs were identified including 99 upregulated genes and 192 downregulated genes. Our results showed that the PPIN of HCC was made up of 287 nodes and 2527 edges. GO analysis showed that these genes were mainly enriched in the molecular function of protein binding. Additionally, KEGG pathway analysis also revealed that DEGs were mainly involved in the metabolic, cell cycle, and chemical carcinogenesis pathways. Interestingly, a significant module with high centrality features including 10 key genes was found. Among these, CDK1, NDC80, HMMR, CDKN3, and PTTG1, which were only upregulated in HCC patients, have attracted much attention. Furthermore, qRT-PCR also confirmed the upregulation of these five key genes in the normal human hepatocyte cell line (HL-7702) and HCC cell lines (SMMC-7721, MHCC-97L, and MHCC-97H); patients with upregulated expression of these five key genes had significantly poorer survival and prognosis. CDK1, NDC80, HMMR, CDKN3, and PTTG1 can be used as molecular markers for HCC. This finding provides potential strategies for clinical diagnosis, accurate treatment, and prognosis analysis of liver cancer.

scholarly journals Bioinformatic Analysis of Circular RNA-Associated ceRNA Network Associated with Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jiacheng Wu ◽  
Shui Liu ◽  
Yien Xiang ◽  
Xianzhi Qu ◽  
Yingjun Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Pathway Analysis ◽  
Target Genes ◽  
Kegg Pathway ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Differentially Expressed ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Kegg Pathway Analysis

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and is associated with a high mortality rate and poor treatment efficacy. In an attempt to investigate the mechanisms involved in the pathogenesis of HCC, bioinformatic analysis and validation by qRT-PCR were performed. Three circRNA GEO datasets and one miRNA GEO dataset were selected for this purpose. Upon combined biological prediction, a total of 11 differentially expressed circRNAs, 15 differentially expressed miRNAs, and 560 target genes were screened to construct a circRNA-related ceRNA network. GO analysis and KEGG pathway analysis were performed for the 560 target genes. To further screen key genes, a protein-protein interaction network of the target genes was constructed using STRING, and the genes and modules with higher degree were identified by MCODE and CytoHubba plugins of Cytoscape. Subsequently, a module was screened out and subjected to GO enrichment analysis and KEGG pathway analysis. This module included eight genes, which were further screened using TCGA. Finally, UBE2L3 was selected as a key gene and the hsa_circ_0009910–miR-1261–UBE2L3 regulatory axis was established. The relative expression of the regulatory axis members was confirmed by qRT-PCR in 30 pairs of samples, including HCC tissues and adjacent nontumor tissues. The results suggested that hsa_circ_0009910, which was upregulated in HCC tissues, participates in the pathogenesis of HCC by acting as a sponge of miR-1261 to regulate the expression of UBE2L3. Overall, this study provides support for the possible mechanisms of progression in HCC.

scholarly journals Disparity of Hepatocellular Carcinoma in Tumor Microenvironment-Related Genes and Infiltrating Immune Cells between Asian and Non-Asian Populations

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1274
Author(s):  
Lien-Hung Huang ◽  
Ting-Min Hsieh ◽  
Chun-Ying Huang ◽  
Yueh-Wei Liu ◽  
Shao-Chun Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Risk Factor ◽  
Liver Cancer ◽  
Immune Cells ◽  
Expression Profiles ◽  
Primary Liver Cancer ◽  
Temporal Variations ◽  
Hcv Infection ◽  
Chronic Alcohol Abuse ◽  
Asian Patients

Hepatocellular carcinoma (HCC) is the most common cause of primary liver cancer deaths worldwide. The major risk factors for liver cancer development are cirrhosis, hepatitis B virus (HBV), hepatitis C virus (HCV) infection, and chronic alcohol abuse. HCC displays heterogeneity in terms of biology, etiology, and epidemiology. In Southeast Asia and Africa, chronic HBV infection is a major risk factor for HCC, whereas chronic HCV infection is a risk factor for HCC in western countries and Japan. Environmental and genetic conditions also play a role in the regional and temporal variations in the incidence of HCC. In this study, we used the ESTIMATE (ESTIMATE, Estimation of stromal and immune cells in malignant tumor tissues using expression data) algorithm and the CIBERSOFT tool to analyze gene expression profiles and infiltrating immune cells in HCC between Asian and non-Asian patients. The results showed that stromal and immune scores were dependent on overall survival (OS) in non-Asian patients but not in Asian patients. Kaplan–Meier survival analysis revealed four differentially expressed genes (DEGs) that were significantly associated with OS in non-Asian patients only. CIBERSORT (CIBERSORT, Cell type identification by estimating relative subsets of known RNA transcripts) analysis indicated that the composition of infiltrating immune cells was significantly different between Asian and non-Asian patients. By parsing the subclasses of HCC, the ability to predict prognosis and guide therapeutic targets for potentially actionable HCC may be improved.

scholarly journals Bioinformatics analysis to identify the key genes affecting the progression and prognosis of hepatocellular carcinoma

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Yingai Zhang ◽  
Shunlan Wang ◽  
Jingchuan Xiao ◽  
Hailong Zhou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Primary Liver Cancer ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Ppi Network ◽  
Sequencing Data ◽  
Protein Coding ◽  
Qrt Pcr ◽  
Protein Coding Genes ◽  
Key Genes

Abstract Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, which has poor outcome. The present study aimed to investigate the key genes implicated in the progression and prognosis of HCC. The RNA-sequencing data of HCC was extracted from The Cancer Genome Atlas (TCGA) database. Using the R package (DESeq), the differentially expressed genes (DEGs) were analyzed. Based on the Cluepedia plug-in in Cytoscape software, enrichment analysis for the protein-coding genes amongst the DEGs was conducted. Subsequently, protein–protein interaction (PPI) network was built by Cytoscape software. Using survival package, the genes that could distinguish the survival differences of the HCC samples were explored. Moreover, quantitative real-time reverse transcription-PCR (qRT-PCR) experiments were used to detect the expression of key genes. There were 2193 DEGs in HCC samples. For the protein-coding genes amongst the DEGs, multiple functional terms and pathways were enriched. In the PPI network, cyclin-dependent kinase 1 (CDK1), polo-like kinase 1 (PLK1), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), serum amyloid A1 (SAA1), and lysophosphatidic acid receptor 3 (LPAR3) were hub nodes. CDK1 interacting with PLK1 and FOS, and LPAR3 interacting with FOS and SAA1 were found in the PPI network. Amongst the 40 network modules, 4 modules were with scores not less than 10. Survival analysis showed that anterior gradient 2 (AGR2) and RLN3 could differentiate the high- and low-risk groups, which were confirmed by qRT-PCR. CDK1, PLK1, FOS, SAA1, and LPAR3 might be key genes affecting the progression of HCC. Besides, AGR2 and RLN3 might be implicated in the prognosis of HCC.

scholarly journals Profiling of tumour-associated microbiota in human hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seiga Komiyama ◽  
Takahiro Yamada ◽  
Nobuyuki Takemura ◽  
Norihiro Kokudo ◽  
Koji Hase ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Fatty Liver Disease ◽  
Primary Liver Cancer ◽  
Epithelial Barrier ◽  
Sequence Variants ◽  
Alcoholic Fatty Liver ◽  
Uncultured Bacterium ◽  
Hepatitis C Viruses ◽  
Alcoholic Fatty Liver Disease

AbstractLiver cancer is the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) is a primary liver cancer that results from chronic hepatitis caused by multiple predisposing factors such as viral infection, alcohol consumption, and non-alcoholic fatty liver disease. Accumulating studies have indicated that dysfunction of the gut epithelial barrier and hepatic translocation of gut microbes may be implicated in the pathogenesis of HCC. However, the translocated bacteria in HCC patients remains unclear. Here, we characterised tumour-associated microbiota in patients with liver cancer and focused on HCC. We observed that the number of amplicon sequence variants in tumour-associated microbiota was significantly higher compared with that in non-tumour regions of the liver. The tumour-associated microbiota consisted of Bacteroidetes, Firmicutes, and Proteobacteria as the dominant phyla. We identified an unclassified genus that belonged to the Bacteroides, Romboutsia, uncultured bacterium of Lachnospiraceae as a signature taxon for primary liver cancer. Additionally, we identified Ruminococcus gnavus as a signature taxon for HCC patients infected with hepatitis B and/or hepatitis C viruses. This study suggests that tumour microbiota may contribute to the pathology of HCC.

scholarly journals The Association between Diet and Hepatocellular Carcinoma: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 172
Author(s):  
Elena S. George ◽  
Surbhi Sood ◽  
Anna Broughton ◽  
Georgia Cogan ◽  
Megan Hickey ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Liver Cancer ◽  
Dietary Pattern ◽  
Quantitative Research ◽  
Primary Liver Cancer ◽  
Healthy Eating Index ◽  
Vitamin B9 ◽  
Related Risk ◽  
Monounsaturated Fats

Globally, liver cancer is the sixth most common cause of cancer mortality, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. Emerging evidence states that diet is recognised as a potential lifestyle-related risk factor for the development of HCC. The aim of this systematic review is to determine whether there is an association between diet and the development of HCC. Using the PRISMA guidelines, three databases (MEDLINE Complete, CINAHL and Embase) were systematically searched, and studies published until July 2020 were included. Thirty observational studies were selected. The protocol was registered with PROSPERO (CRD42019135240). Higher adherence to the Mediterranean dietary pattern, Alternative Healthy Eating Index-2010, the Urban Prudent Dietary Pattern, the Traditional Cantonese Dietary Pattern, intake of vegetables, wholegrains, fish, poultry, coffee, macronutrients such as monounsaturated fats and micronutrients such as vitamin E, vitamin B9, β-carotene, manganese and potassium were associated with a reduced risk of HCC. The results suggest a potential role of diet in the development of HCC. Further quantitative research needs to be undertaken within a range of populations to investigate diet and the relationship with HCC risk.

scholarly journals The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3740
Author(s):  
Chunye Zhang ◽  
Ming Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Fatty Liver ◽  
Early Stage ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Underlying Mechanism ◽  
Diagnostic Methods ◽  
T Cell Therapy ◽  
Nonalcoholic Fatty Liver

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.

scholarly journals Circular RNA Hsa_Circ_0091579 Serves as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

2018 ◽  
Vol 51 (1) ◽  
pp. 290-300 ◽  
Author(s):  
Chenxing Zhang ◽  
Chenyue Zhang ◽  
Jiamao Lin ◽  
Haiyong Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Expression Profiles ◽  
Critical Role ◽  
Roc Curves ◽  
Altered Expression ◽  
Qrt Pcr ◽  
Specificity And Sensitivity ◽  
Tumor Tissues ◽  
Potential Biomarker

Background/Aims: An increasing number of studies have suggested that circular RNAs (circRNAs) have vital roles in carcinogenesis and tumor progression. However, the function of circRNAs in hepatocellular carcinoma (HCC) remains poorly characterized. Methods: We investigated the levels of circRNAs in patients with HCC to identify potential diagnostic biomarkers. We examined circRNA expression profiles in liver tumors and paired non-cancerous liver tissues from three HCC patients with cancer thrombus using a circRNA microarray. Bioinformatics analysis was performed to find circRNAs with significantly altered expression levels between tumors and their paired non-tumor tissues. We confirmed our initial findings by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves were also applied to identify a candidate circRNA with the optimal specificity and sensitivity. Finally, X-tile software was adopted to calculate the most efficient cut-off value for hsa_circ_0091579 expression. Results: Microarray analysis identified 20 unique circRNAs that were differentially expressed between tumor and non-tumor tissues (P < 0.05). The expression of these 20 circRNAs was verified by qRT-PCR. The expression of hsa_circ_16245-1 and hsa_circ_0091579 mRNA was consistent with their levels as tested by the microarray. The ROC curves showed that both hsa_circ_16245-1 and hsa_circ_0091579 had favorable specificity and sensitivity. We further confirmed that hsa_circ_0091579 was significantly upregulated in HCC and its high expression was intimately associated with a worse overall survival in patients with HCC. Conclusion: Hsa_circ_0091579 may play a critical role in HCC progression and serve as a potential biomarker for the prognosis of patients with HCC.

scholarly journals 452 Preliminary analysis of a real-world study (RWS) of camrelizumab treatment in primary liver cancer (PLC)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A479-A480
Author(s):  
Zhendong Chen ◽  
Nianfei Wang ◽  
Dayong Luo ◽  
Bo Jiang ◽  
Mu Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Group Performance ◽  
Primary Liver Cancer ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Open Label ◽  
Patient Disposition ◽  
Ecog Ps

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the landscape of PLC management at all evolutionary stages.1 As an anti-programmed cell death-1 (PD-1) antibody, camrelizumab monotherapy and in combination with apatinib, an anti-angiogenetic tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-2, chemotherapy or locoregional therapy, have demonstrated their efficacy in advanced hepatocellular carcinoma (HCC).2 3 4 5MethodsThis prospective, open-label, multi-center, observational RWS was conducted to evaluate efficacy and safety of camrelizumab in treatment of PLC in clinical practice. Eligible patients were histopathologically or cytologically identified HCC or intrahepatic cholangiocarcinoma, who were going to receive camrelizumab treatment, with age ≥18 ages, Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0–2 and Child-Pugh score ≤ 9. Patients were treated at clinician discretion. Three hundred patients were planned to enroll, including advanced or peri-operative PLC. The primary endpoint was progress-free survival for advanced PLC, whose efficacy was available to analysis. Efficacy was assessed per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsFrom March 29, 2020 to June 10, 2021,a total of 147 eligible patients of advanced PLC were enrolled and included in this interim analysis, with 128 (87.1%) men, 130 (94.9%) ECOG PS of 0–1, 139 (94.6%) HCC, 74 (50.4%) Barcelona Clinic Liver Cancer stage C, 98 (66.7%) Child-Pugh B, and 72 (49.0%) with extrahepatic metastases, shown in table 1. Of the 147 patients, 45 (30.1%) patients were treated with camrelizumab monotherapy, 79 (53.8%) patients with combination with angiogenesis inhibitors, of which 55 (37.4%) in combination with apatinib, 21 (14.3%) patients with camrelizumab and chemotherapy. Patients, who had at least one efficacy assessment, were included in the efficacy analyses. Up to July 19, 2021, with a median follow time of 6.2 months, 132 patients were available for efficacy analyses. Patient disposition was shown in figure 1. Objective response rate (ORR) and disease control rate (DCR) were 10%/30.8%/35.3% and 75.0%/86.5%/70.6% in camrelizumab monotherapy/combined with apatinib/combined with chemotherapy, respectively. (table 2) The most common camrelizumab-treatment related adverse events (AEs) included reactive cutaneous capillary endothelial proliferation (RCCEP) (12, 8.2%), ICI-induced pneumonia (2, 1.4%), enterocolitis (2, 1.4%), and nephritis (1, 0.7%), of which all these AEs recovered. Other AEs included increase of transaminase (5, 3.4%) and hypertension (4, 2.7%). All AEs were 1–2 grade and no treatment-related death occurred.Abstract 452 Table 1Baseline characteristicsAbstract 452 Figure 1Patient dispositionAbstract 452 Table 2Confirmed tumor response assessed by investigators per RECIST v1.1ConclusionsCamrelizumab, combined with anti-angiogenetic agents or chemotherapy, or monotherapy, demonstrated good efficacy and safety in treatment of PLC.Trial RegistrationChiCTR2000034264ReferencesLlovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7(1):6–28.Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol 2020;21(4):571–580.Xu J, Shen J, Gu S, et al. Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial. Clin Cancer Res 2021;27(4):1003–1011.Mei K, Qin S, Chen Z, et al. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial. J Immunother Cancer 2021;9(3).Qin S, Bai Y, Lim HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol 2013;31(28):3501–3508.Ethics ApprovalThis study was approved by China registered clinical trial ethics review committee with No.ChiECRCT20200042.

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