scholarly journals Prognostic roles of the transcriptional expression of exportins in hepatocellular carcinoma

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Lubiao Chen ◽  
Yanlin Huang ◽  
Liang Zhou ◽  
Yifan Lian ◽  
Jialiang Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Data ◽  
Disease Free Survival ◽  
Dna Amplification ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
High Expression ◽  
Poor Overall Survival ◽  
Cancer Tissues

Abstract Aims: A large number of studies have suggested that exportins (XPOs) play a pivotal role in human cancers. In the present study, we analyzed XPO mRNA expression in cancer tissues and explored their prognostic value in hepatocellular carcinoma (HCC). Methods: Transcriptional and survival data related to XPO expression in HCC patients were obtained through the ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Gene Expression Profiling Interactive Analysis (GEPIA). Sequence alteration data for XPOs were obtained from The Cancer Genome Atlas (TCGA) database and c-BioPortal. Gene functional enrichment analyses were performed with Database for Annotation, Visualization and Integrated Discovery (DAVID). Results: Compared with normal liver tissues, significant XPO mRNA overexpression was observed in HCC cancer tissues. There was a trend of higher XPO expression in more advanced clinical stages and lower differentiated pathological grades of HCC. In HCC patients, high expression of XPO1, CSE1L, XPOT, XPO4/5/6 was related to poor overall survival (OS), and XPO1, CSE1L and XPO5/6 were correlated with poor disease-free survival (DFS). The main genetic alterations in XPOs involved mRNA up-regulation, DNA amplification and deletion. General XPO mutations were remarkably associated with worse OS and mostly affected the pathways of RNA transport and oocyte meiosis. Conclusion: High expression of XPOs was associated with a poor prognosis in HCC patients. XPOs may be exploited as good prognostic biomarkers for survival in HCC patients.

scholarly journals Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 217-223
Author(s):  
Xin Song ◽  
Shidong Zhang ◽  
Run Tian ◽  
Chuanjun Zheng ◽  
Yuge Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transmembrane Domain ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Chi Square ◽  
Tumor Tissues ◽  
The Relationship ◽  
Low Expression

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

scholarly journals High Expression of ANXA2 Pseudogene ANXA2P2 Promotes an Aggressive Phenotype in Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Qiu-shuang Wang ◽  
Liang-Liang Shi ◽  
Fei Sun ◽  
Yi-fan Zhang ◽  
Ren-Wang Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Free Survival ◽  
Annexin A2 ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Migration And Invasion ◽  
Targeted Drugs ◽  
Noncancerous Tissue ◽  
Expression Levels ◽  
Hcc Cells

Objective. Accumulating evidence suggests that pseudogenes play potential roles in the regulation of their cognate wild-type genes, oncogenes, and tumor suppressor genes. ANXA2P2 (annexin A2 pseudogene 2) is one of three pseudogenes of annexin A2 that have recently been shown to be aberrantly transcribed in hepatocellular carcinoma (HCC) cells. However, its clinical meaning and biological function in HCC have remained unclear. Therefore, the present study was aimed at exploring the prognostic value of a high expression of ANXA2P2 in HCC tissue and at identifying whether it can affect the efficacy of targeted drugs (sorafenib, regorafenib, and lenvatinib). Methods. We obtained ANXA2P2 mRNA expression levels from The Cancer Genome Atlas (TCGA) RNA sequence database. The expression levels of ANXA2P2 in 49 pairs of intratumoral and peritumoral liver tissues were examined by RT-PCR. Wound healing and transwell assays were performed to confirm the tumor-promoting properties of ANXA2P2 in HCC cells. CCK8 assay was conducted to identify whether ANXA2P2 can affect the growth of HCC cells when administered with targeted drugs (sorafenib, regorafenib, and lenvatinib). Results. The expression of ANXA2P2 in HCC tissues was significantly higher than that in adjacent cancerous tissues from TCGA database and validation group. Additionally, patients with high ANXA2P2 expression in HCC tissue had a shorter overall survival, whereas no statistically significant correlation was found between ANXA2P2 expression and disease-free survival (p=0.08) as well as other clinical parameters, such as age, gender, histological grade, T classification, stage, albumin level, alpha-fetoprotein, and vascular invasion (p=0.7323, 0.8807, 0.5762, 0.8515, 0.7113, 0.242, 1.0000, and 0.7685, respectively). Furthermore, in vitro experiments showed that knockdown of ANXA2P2 inhibited migration and invasion of HCC cells but did not have an influence on the HCC cell proliferation when treated with targeted drugs (sorafenib, regorafenib, and lenvatinib). Conclusion. Our study confirmed elevated ANXA2P2 expression levels in HCC tissue compared with adjacent noncancerous tissue and a worse prognosis of patients with high ANXA2P2 levels in the HCC tissue. The newly found properties of promoting migration and invasion of ANXA2P2 in HCC help to explain this phenomenon. ANXA2P2 could be a novel and suitable predicative biomarker for the risk assessment of recurrence or metastasis of HCC patients but may not be effective to predict the efficacy of targeted drugs.

scholarly journals High SGO2 Expression Predicts Poor Overall Survival: A Potential Therapeutic Target for Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 876
Author(s):  
Min Deng ◽  
Shaohua Li ◽  
Jie Mei ◽  
Wenping Lin ◽  
Jingwen Zou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Therapeutic Target ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Clinicopathological Parameters ◽  
Potential Therapeutic Target ◽  
Poor Overall Survival

Shugoshin2 (SGO2) may participate in the occurrence and development of tumors by regulating abnormal cell cycle division, but its prognostic value in hepatocellular carcinoma (HCC) remains unclear. In this study, we accessed The Cancer Genome Atlas (TCGA) database to get the clinical data and gene expression profile of HCC. The expression of SGO2 in HCC tissues and nontumor tissues and the relationship between SGO2 expression, survival, and clinicopathological parameters were analyzed. The SGO2 expression level was significantly higher in HCC tissues than in nontumor tissues (p < 0.001). An analysis from the Oncomine and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases also demonstrated that SGO2 was upregulated in HCC (all p < 0.001). A logistic regression analysis revealed that the high expression of SGO2 was significantly correlated with gender, tumor grade, pathological stage, T classification, and Eastern Cancer Oncology Group (ECOG) score (all p < 0.05). The overall survival (OS) of HCC patients with higher SGO2 expression was significantly poor (p < 0.001). A multivariate analysis showed that age and high expression of SGO2 were independent predictors of poor overall survival (all p < 0.05). Twelve signaling pathways were significantly enriched in samples with the high-SGO2 expression phenotype. Ten proteins and 34 genes were significantly correlated with SGO2. In conclusion, the expression of SGO2 is closely related to the survival of HCC. It may be used as a potential therapeutic target and prognostic marker of HCC.

scholarly journals Correlation Between Prognostic Biomarker SLC1A5 and Immune Infiltrates in Various Types of Cancers Including Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Junsheng Zhao ◽  
Zhongli Yang ◽  
Mingmin Tu ◽  
Wei Meng ◽  
Hainv Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Immunity ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Poor Overall Survival ◽  
Normal Tissues ◽  
Multiple Cancers

BackgroundSolute carrier family 1 member 5 (SLC1A5) is a major glutamine transporter and plays a key role in tumor growth. The main objectives of this study were to visualize the prognostic landscape of SLC1A5 in multiple cancers and determine the relations between SLC1A5 expression and tumor immunity.MethodsSLC1A5 expression and its effect on tumor prognosis were analyzed using multiple online tools Oncomine, Gene Expression Profiling Interactive Analysis, PrognoScan, and Kaplan-Meier plotter with their own datasets as well as the data from The Cancer Genome Atlas. The correlations between SLC1A5 and tumor immune infiltrates were determined via TIMER.ResultsSLC1A5 expression was significantly higher in several types of cancers, including hepatocellular carcinoma (HCC), compared with corresponding normal tissues. High SLC1A5 expression correlated with poor overall survival and with disease-free survival related to alcohol consumption. Moreover, SLC1A5 expression correlated positively with the numbers of tumor-infiltrating B cells, CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells in HCC and in lower-grade glioma (LGG). Also, SLC1A5 expression showed strong correlations with diverse immune marker sets in HCC and LGG, indicating its role in regulating tumor immunity.ConclusionsSLC1A5 represents a useful prognostic biomarker in multiple cancers, and its expression correlates highly with tumor immune-cell infiltration, especially in HCC and LGG.

scholarly journals Low APOA-1 Expression in Hepatocellular Carcinoma Patients Is Associated With DNA Methylation and Poor Overall Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingyun Guo ◽  
Binglu Huang ◽  
Ruixue Li ◽  
Jiao Li ◽  
Shan Tian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Overall Survival ◽  
Survival Data ◽  
The Cancer Genome Atlas ◽  
High Density Lipoproteins ◽  
Healthy Individuals ◽  
Poor Overall Survival ◽  
Strong Negative Correlation ◽  
Free Survival

Background: Hepatocellular carcinoma (HCC) is the most frequent fatal malignancy, and it has a poor prognosis. Apolipoprotein 1 (APOA-1), the main protein component of high-density lipoproteins, is involved in numerous biological processes. Thus, this study was performed to detect the clinical significance of APOA-1 mRNA, APOA-1 expression, and APOA-1DNA methylation in patients with HCC.Methods: Data mining was performed using clinical and survival data from the Cancer Genome Atlas (TCGA) and Oncomine databases. The serum concentration of APOA-1 was measured in 316 patients with HCC and 100 healthy individuals at Renmin Hospital of Wuhan University, and the intact clinical information was reviewed and determined using univariate and multivariate Cox hazard models.Results: Bioinformatic analysis revealed that APOA-1 mRNA was present at lower levels in the serum of patients with HCC than in that of healthy individuals, and there was a strong negative correlation between levels of APOA-1 mRNA and APOA-1 DNA methylation. High expression of APOA-1 transcription correlated with better overall survival (p = 0.003), and APOA-1 hypermethylation correlated with progress-free survival (p = 0.045) in HCC sufferers. Next, the clinical data analysis demonstrated that APOA-1 protein levels in the serum were significantly lower in patients with HCC than in healthy controls. Furthermore, the expression of APOA-1 was significantly associated with some significant clinical indexes, and elevated APOA-1 expression was significantly associated with favorable (OS; HR:1.693, 95% CI: 1.194–2.401, p = 0.003) and better progression-free survival (PFS; HR = 1.33, 95% CI = 1.194–2.401, p = 0.045). Finally, enrichment analysis suggested that co-expressed genes of APOA-1 were involved in lipoprotein metabolism and FOXA2/3 transcription factor networks.Conclusion: APOA-1 mRNA expression is negatively regulated by DNA methylation in HCC. Low expression of APOA-1 might be a potential risk biomarker to predict survival in patients with HCC.

scholarly journals Identification of Ten-lncRNA Signatures Predict Disease-free and Overall Survival for Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Si-shu Yang ◽  
Jiong Lu ◽  
Xian-ze Xiong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Mitogen Activated Protein Kinase ◽  
Pathway Enrichment Analysis ◽  
Disease Free

Abstract Background: The prognosis of hepatocellular carcinoma (HCC) is bleak though it has been improved over recent years. Early diagnosis could improve the survival. Plenty of researches indicate that long non-coding RNAs (lncRNAs) could play an important role in prognostic prediction of cancer as a kind of biomarker. Results: We identified and validated ten-lncRNAs based signatures to predict disease-free survival (DFS) and overall survival (OS) of HCC respectively from lncRNA expression data of HCC patients in The Cancer Genome Atlas (TCGA) database. Stratified survival analysis showed that the performance of lncRNAs related signatures was better than tumor, node, metastasis(TNM) staging system. Functional enrichment analysis showed that organelle fission and regulation of mRNA metabolic process were significantly enriched in differentially expressed lncRNAs (DElncRNAs). Transcriptional misregulation in cancer and mitogen-activated protein kinase (MAPK) signaling pathway were significantly enriched pathways in the pathway enrichment analysis. Conclusion: we constructed two lncRNAs based signatures which could predict prognosis of HCC more accurate than the traditional ways.

scholarly journals Upregulated Seizure-Related 6 Homolog-Like 2 Is a Prognostic Predictor of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Linhe Wang ◽  
Xiangchao Ling ◽  
Caihui Zhu ◽  
Zhiheng Zhang ◽  
Ziming Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Prognostic Predictor ◽  
Qrt Pcr ◽  
Cancer Genome Atlas

Seizure-related 6 homolog-like 2 (SEZ6L2), which is localized on the cell surface, has been found to be associated with tumor angiogenesis and lung cancer progression. However, the role of SEZ6L2 in hepatocellular carcinoma (HCC) is still unclear. We obtained data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to investigate SEZ6L2 expression and regulation in HCC. Then, HCC tissue samples were collected to verify SEZ6L2 by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining (IHC). Patient information was collected for survival and prognosis analysis. qRT-PCR, IHC, and bioinformatics analysis showed that the SEZ6L2 protein was highly expressed in HCC samples. Clinical data showed that high SEZ6L2 protein expression was correlated with tumor-node-metastasis (TNM) stages (P=0.046), tumor number (P=0.016), and tumor size (P=0.029). Meanwhile, SEZ6L2 overexpression was closely associated with poor overall survival and disease-free survival in HCC patients. Moreover, SEZ6L2 is an independent prognostic predictor for the survival of HCC patients. This study suggests a significant correlation between SEZ6L2 and HCC, which means that SEZ6L2 may potentially serve as a useful prognostic biomarker for HCC patients.

scholarly journals Identifies Oncogene PDRG1 as a Potential Prognostic Biomarker in Hepatocellular Carcinoma: A Study Based on Bioinformatics Analysis

2021 ◽  
Author(s):  
Jianyang Lin ◽  
Xin Ding ◽  
Zhihong Chen ◽  
Huiwen Pan ◽  
Yinyan Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Survival Rates ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Th2 Cells ◽  
Poor Overall Survival ◽  
Bioinformatics Analyses ◽  
Malignant Liver Tumor ◽  
Ppi Networks

Abstract Background: Hepatocellular carcinoma (HCC) is globally recognized as one of the most frequently occurring primary malignant liver tumor, making the identification of HCC biomarkers critically important. Methods: The gene expression and clinicopathology analysis, GO enrichment analysis (GSEA) and immune infiltration analysis are based on data obtained from The Cancer Genome Atlas (TCGA), with additional bioinformatics analyses performed. The statistical analysis was conducted in R. The protein-protein interaction (PPI) networks was constructed and the module analysis was performed using STRING and Cytoscape. Construction and evaluation of prognostic model based on PDRG1 and tumor status used nomogram and calibration.Results: The expression of PDRG1 was significantly higher in HCC tumor tissues. High expression of PDRG1 in HCC patients was significantly correlated with poor Overall Survival and adverse clinicopathological features including advanced T stage, residual tumor, histologic grade, vascular invasion, TP53 status and AFP level. GO, GSEA revealed that PDRG1 was closely correlated with DNA repair, DNA replication and cell cycle. Spearman correlation showed high expression of PDRG1 was significantly correlated with Th2 cells level in HCC patients. Nomograms based on PDRG1 and tumor stage had good predictive performance on overall survival rates of HCC patients.Conclusions: Our study demonstrated the potential significance of PDRG1 expression in the diagnosis and prognosis of HCC and further explored the function in HCC. Further study is still needed to confirm these results. The underlying mechanism revealed by these results provides a basis for PDRG1 as a new molecular target for the prevention and treatment of HCC.

scholarly journals A Comprehensive Analysis of the MAGE Family as Prognostic and Diagnostic Markers for Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Rong Li ◽  
Jiao Gong ◽  
Cuicui Xiao ◽  
Shuguang Zhu ◽  
Zhongying Hu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Clinical Stage ◽  
Enrichment Analysis ◽  
Tumor Grade ◽  
Functional Enrichment Analysis ◽  
Genetic Alterations ◽  
Diagnostic Markers ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment

Abstract Background: The Melanoma Antigen Gene (MAGE) family is a large, highly conserved group of proteins that share a common MAGE homology domain. Multiple MAGEs are aberrantly expressed in a variety of cancers. However, the function of distinct MAGE genes in hepatocellular carcinoma (HCC) is largely unclear. Our study aimed to comprehensively analyze the MAGE family as prognostic and diagnostic markers for HCC. Methods: In this research, all HCC data were obtained from NCBI GEO DataSets, The Cancer Genome Atlas (TCGA) and our clinical center. UALCAN was used to reveal the expression profile of distinct MAGEs in HCC and further evaluate the association between the expression of MAGEs and the clinicopathological characteristics of HCC patients, including clinical stage, tumor grade. Kaplan-Meier Plotter (KM-Plot) was used to evaluate the correlation between MAGEs expression and the overall survival (OS) of HCC patients. qRT-PCR was used to detection the expression levels of MAGEs in HCC samples. cBioPortal was used to analyze the genetic alterations in MAGEs and their associations with OS of HCC patients. Gene Set Variation Analysis (GSVA) algorithm was used to do functional enrichment analysis of MAGE genes in HCC to reveal the molecular mechanisms of MAGEs functioned in HCC. Results: Our research showed that many MAGE genes were dysregulated in HCC and most of them were highly expressed. Among them, MAGEA1、MAGEC2、MAGED1、MAGED2、MAGEF1 and MAGEL2 were significantly correlated with clinical stage and differentiation of HCC patients. MAGED1、MAGED2、MAGEA6、MAGEA12、MAGEA10、MAGEB4、MAGEL2 and MAGEC3 had significant correlation with HCC prognosis. Further functional enrichment analysis suggested the dysregulated MAGEs may play important roles in signal transduction. Conclusions: Taken together, our research revealed that multiple MAGEs were dysregulated in HCC and they might play important roles in the development of HCC and can be exploited as useful biomarkers for diagnosis and treatment for HCC.

scholarly journals Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Chen Yu ◽  
Xiang-Yi Chen ◽  
Xin Li ◽  
Hai-Yu Zhou ◽  
De-Quan Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Complex ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Prognostic Biomarkers ◽  
High Expression

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

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