scholarly journals The prognostic value of LINC01296 in pan-cancers and the molecular regulatory mechanism in hepatocellular carcinoma: a comprehensive study based on data mining, bioinformatics, and in vitro validation

2019 ◽  
Vol Volume 12 ◽  
pp. 5861-5885 ◽  
Author(s):  
Chaojie Liang ◽  
Yongping Zhang ◽  
Yu Zhang ◽  
Ruihuan Li ◽  
Zhimin Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Data Mining ◽  
Prognostic Value ◽  
Regulatory Mechanism ◽  
Comprehensive Study

Role of BCYRN1 in hepatocellular carcinoma pathogenesis by lncRNA–miRNA–mRNA network analysis and its diagnostic and prognostic value

Epigenomics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1209-1231 ◽  
Author(s):  
Xin-Liang Ming ◽  
Yan-Lin Feng ◽  
Ding-Dong He ◽  
Chang-Liang Luo ◽  
Jia-Ling Rong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Data Mining ◽  
Microarray Data ◽  
Prognostic Value ◽  
Prognostic Biomarker ◽  
Tumor Node Metastasis ◽  
Comprehensive Strategy ◽  
Node Metastasis ◽  
Diagnostic And Prognostic Value

Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results: BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA–miRNA–mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.

scholarly journals CDT1 Is a Novel Prognostic and Predictive Biomarkers for Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Chenhui Cai ◽  
Ying Zhang ◽  
Xu Hu ◽  
Wenhui Hu ◽  
Sizhen Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Replication ◽  
Tissue Microarray ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Predictive Biomarkers ◽  
Transcriptional Level ◽  
Abnormal Expression

ObjectiveHepatocellular carcinoma (HCC) is one of the most common malignant tumors endangering human health and life in the 21st century. Chromatin licensing and DNA replication factor 1 (CDT1) is an important regulator of DNA replication licensing, which is essential for initiation of DNA replication. CDT1 overexpression in several human cancers reportedly leads to abnormal cell replication, activates DNA damage checkpoints, and predisposes malignant transformation. However, the abnormal expression of CDT1 in HCC and its diagnostic and prognostic value remains to be elucidated.MethodsTCGA, ONCOMINE, UALCAN, HCCDB, HPA, Kaplan-Meier plotter, STRING, GEPIA, GeneMANIA, and TIMER were conducted for bioinformatics analysis. CDT1 protein expression was evaluated by immunohistochemistry in HCC tissues through a tissue microarray. qRT-PCR, western blot and a cohort of functional experiments were performed for in vitro validation.ResultsIn this study, we discovered remarkably upregulated transcription of CDT1 in HCC samples relative to normal liver samples through bioinformatic analysis, which was further verified in clinical tissue microarray samples and in vitro experiments. Moreover, the transcriptional level of CDT1 in HCC samples was positively associated with clinical parameters such as clinical tumor stage. Survival, logistic regression, and Cox regression analyses revealed the significant clinical prognostic value of CDT1 expression in HCC. The receiver operating characteristic curve and nomogram analysis results demonstrated the strong predictive ability of CDT1 in HCC. Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analyses indicated that CDT1 was mainly associated with the cell cycle, DNA repair, and DNA replication. We further demonstrated the significant correlation between CDT1 and minichromosome maintenance (MCM) family genes, revealing abnormal expression and prognostic significance of MCMs in HCC. Immune infiltration analysis indicated that CDT1 was significantly associated with immune cell subsets and affected the survival of HCC patients. Finally, knockdown of CDT1 decreased, whereas overexpression of CDT1 promoted the proliferation, migration, invasion of HCC cells in vitro.ConclusionsOur study findings demonstrate the potential diagnostic and prognostic significance of CDT1 expression in HCC, and elucidate the potential molecular mechanism underlying its role in promoting the occurrence and development of liver cancer. These results may provide new opportunities and research paths for targeted therapies in HCC.

scholarly journals Identification of Prognostic Glycolysis-Related lncRNA Signature in Tumor Immune Microenvironment of Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Yang Bai ◽  
Haiping Lin ◽  
Jiaqi Chen ◽  
Yulian Wu ◽  
Shi’an Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Risk Score ◽  
Prognostic Value ◽  
Enrichment Analysis ◽  
Immune Microenvironment ◽  
Prognostic Accuracy ◽  
Tumor Immune Microenvironment ◽  
Cox Analysis

Purpose: The purpose of this study was to construct a novel risk scoring model with prognostic value that could elucidate tumor immune microenvironment of hepatocellular carcinoma (HCC).Samples and methods: Data were obtained through The Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis were carried out to screen for glycolysis-related long noncoding RNAs (lncRNAs) that could provide prognostic value. Finally, we established a risk score model to describe the characteristics of the model and verify its prediction accuracy. The receiver operating characteristic (ROC) curves of 1, 3, and 5 years of overall survival (OS) were depicted with risk score and some clinical features. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and CIBERSORT analysis were employed to reveal the characteristics of tumor immune microenvironment in HCC. The nomogram was drawn by screening indicators with high prognostic accuracy. The correlation of risk signature with immune infiltration and immune checkpoint blockade (ICB) therapy was analyzed. After enrichment of related genes, active behaviors and pathways in high-risk groups were identified and lncRNAs related to poor prognosis were validated in vitro. Finally, the impact of MIR4435-2HG upon ICB treatment was uncovered.Results: After screening through multiple steps, four glycolysis-related lncRNAs were obtained. The risk score constructed with the four lncRNAs was found to significantly correlate with prognosis of samples. From the ROC curve of samples with 1, 3, and 5 years of OS, two indicators were identified with high prognostic accuracy and were used to draw a nomogram. Besides, the risk score significantly correlated with immune score, immune-related signature, infiltrating immune cells (i.e. B cells, etc.), and ICB key molecules (i.e. CTLA4,etc.). Gene enrichment analysis indicated that multiple biological behaviors and pathways were active in the high-risk group. In vitro validation results showed that MIR4435-2HG was highly expressed in the two cell lines, which had a significant impact on the OS of samples. Finally, we corroborated that MIR4435-2HG had intimate relationship with ICB therapy in hepatocellular carcinoma.Conclusion: We elucidated the crucial role of risk signature in immune cell infiltration and immunotherapy, which might contribute to clinical strategies and clinical outcome prediction of HCC.

scholarly journals WASF2 Overexpression and Promoter Hypomethylation Are Associated With Poor Clinical Outcomes in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Hye Ri Ahn ◽  
Geum Ok Baek ◽  
Moon Gyeong Yoon ◽  
Ju A Son ◽  
Jung Hwan Yoon ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regulatory Mechanism ◽  
Cpg Island ◽  
Methylation Status ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Hcc Cells

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Wiskott-Aldrich syndrome protein family member 2 (WASF2) is an integral member of the actin cytoskeleton pathway that plays a crucial role in cell motility. In this study, we aimed to explore the role of WASF2 in HCC carcinogenesis and its regulatory mechanism. Methods: WASF2 expression in HCC was analyzed using six public RNA-seq datasets and 66 paired tissues from patients with HCC. Role of WASF2 in HCC cell phenotypes was evaluated using small interfering RNA (siRNA) in vitro and in vivo. Epigenetic regulatory mechanism of WASF2 was assessed in the Cancer Genome Atlas liver hepatocellular carcinoma project (TCGA_LIHC) dataset and also validated in 38 paired HCC tissues. Results: WASF2 is overexpressed in HCC and is clinically correlated with prognosis. WASF2 inactivation decreased the viability, growth, proliferation, migration, and invasion of Huh-7 and SNU475 HCC cells by restoring G2/M checkpoint function, inducing cell death, and inhibiting epithelial-mesenchymal transition, and hindering actin polymerization. In addition, WASF2 knockdown using siWASF2 in a xenograft mouse model exerted tumor suppressive effect. Furthermore, we observed a negative correlation between WASF2 methylation status and mRNA expression. The cg24162579 CpG island in the WASF2 5′ promoter region was hypomethylated in HCC compared to matched non-tumor samples. Patients with high WASF2 methylation and low WASF2 expression displayed the highest overall survival.Conclusions: WASF2 is overexpressed and hypomethylated in HCC and correlates with patient prognosis. Moreover, WASF2 inactivation exerts anti-tumorigenic effects on HCC cells in vitro and in vivo, suggesting that WASF2 could be a potential therapeutic target for HCC.

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