scholarly journals Mast Cells Resting-Related Prognostic Signature in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hao Zhang ◽  
Lin Sun ◽  
Xiao Hu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mast Cells ◽  
Liver Cancer ◽  
Differentially Expressed Genes ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Immune Checkpoints ◽  
New Ideas ◽  
Cancer Genome Atlas

The immune microenvironment of liver cancer is of great significance for the treatment of liver cancer. After evaluating the content of mast cells resting in the transcriptome data of The Cancer Genome Atlas database by CIBERSORT analysis, this study aimed to group the samples according to the content of mast cells resting in different samples to find the differentially expressed genes in the two groups. Significant prognostic differences were found between high and low mast cells resting infiltration groups. The prognostic model was constructed according to the differentially expressed genes. The model was validated using external independent datasets. The results revealed that the constructed model was reliable. It could well distinguish the prognostic differences of patients in different characteristic groups. The high-risk group was mainly concentrated in metabolic pathways. The risk score of this model was closely related to some immune cells, immune function, and immune checkpoints. Therefore, this model may provide new ideas for immunotherapy of hepatocellular carcinoma.

scholarly journals BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

2022 ◽  
Vol 8 ◽  
Author(s):  
Jianhui Li ◽  
Xiaojuan Tian ◽  
Ye Nie ◽  
Ying He ◽  
Wenlong Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Tumor Infiltrating Lymphocytes ◽  
Normal Liver ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Phosphatase 2A ◽  
Cancer Genome Atlas ◽  
Infiltrating Lymphocytes ◽  
The Impact

Background: BTBD10 serves as an activator of Akt family members through decreasing the protein phosphatase 2A-mediated dephosphorylation. The present study attempted to investigate the prognostic value of BTBD10 in hepatocellular carcinoma (HCC), specially, its relationship with tumor-infiltrating lymphocytes (TILs).Methods: BTBD10 expression was evaluated in HCC using The Cancer Genome Atlas (TCGA) and Xijing Hospital database, and verified in HCC cell lines. Cox analyses were performed to analyze independent prognostic risk factors for HCC. The optimal cut-off value of BTBD10 was calculated, by which all patients were divided into two groups to compare the overall survival (OS). The signaling pathways were predicted, by which BTBD10 may affect the progression of HCC. To investigate the impact of BTBD10 on HCC immunotherapy, correlations between BTBD10 and TILs, immune checkpoints, m6A methylation-related genes and ferroptosis-related genes were assessed. The distribution of half-maximal inhibitory concentration (IC50) of diverse targeted drugs was observed based on the differential expression of BTBD10.Results: BTBD10 expression was higher in HCC tissues and cell lines than that of normal liver tissues and cells. The patients with high expression of BTBD10 showed a worse OS, as compared to that of BTBD10 low-expressing group. Cox analyses indicated that BTBD10 was an independent prognostic risk factor for HCC. Several molecular pathways of immune responses were activated in HCC patients with high-expressing of BTBD10. Furthermore, BTBD10 expression was demonstrated to be positively correlated with tumor-infiltrating B cells, T cells, macrophages, neutrophils and dendritic cells. Meanwhile, the expression of BTBD10 was synchronized with that of several m6A methylation-related genes, ferroptosis-related genes and immune checkpoints. The IC50 scores of Sorafenib, Navitoclax, Veliparib, Luminespib, and Imatinib were found to be lower in BTBD10 high-expressing HCC group.Conclusion: BTBD10 negatively regulates tumor immunity in HCC and exhibits adverse effect on the prognosis of HCC, which could be a potential target for immunotherapy.

scholarly journals Identifying Differentially Expressed MicroRNAs Between Cirrhotic and Non-Cirrhotic Hepatocellular Carcinoma and Exploring Their Functions Using Bioinformatic Analysis

2018 ◽  
Vol 48 (4) ◽  
pp. 1443-1456 ◽  
Author(s):  
Ying Mei ◽  
Yu You ◽  
Jin Xia ◽  
Jian-Ping Gong ◽  
Yun-Bing Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Online Tools ◽  
Tumor Stages ◽  
Differentially Expressed Mirnas ◽  
Cancer Genome Atlas ◽  
Cirrhotic Patients ◽  
Independent Risk Factors

Background/Aims: Few studies have been designed to directly investigate the exact mechanisms underlying the different phenotypes between cirrhotic and non-cirrhotic hepatocellular carcinoma (HCC). This study aimed to illuminate the incidence and developmental mechanisms for both types of HCC through differentially expressed microRNAs (miRNAs) using bioinformatic analysis. Methods: The miRNA-seq data and clinical data of patients (from The Cancer Genome Atlas (TCGA) database) were utilized to determine differentially expressed miRNAs between cirrhotic and non-cirrhotic HCC. Afterwards, the function of the selected miRNAs was predicted with online tools. Furthermore, the miRNA expression and clinical significance were validated by external datasets and our experiment. Results: The present study included 135 non-cirrhotic and 80 cirrhotic patients to find differentially expressed miRNAs. Among them, four miRNAs (mir-1296, mir-23c, mir-149, and mir-95) were finally selected for further validation and analysis. Correlation analysis found that two miRNAs are greatly associated with the non-cirrhotic HCC patients’ clinical traits, such as the T, M, and N tumor stages. However, only mir-23c was associated with the cirrhotic HCC patients’ tumor T and N stages. Furthermore, survival analysis revealed that increased mir-149 in non-cirrhotic HCC, patients’ age and the existence of vessels in the tumor in cirrhotic HCC were independent risk factors for the patients’ postoperative overall survival. Functional and interaction analyses also supported the notion that these miRNAs function through some pathways that influence the behavior of the HCC. These results are strongly supported by analysis of extra datasets and our experiment. Conclusions: The cirrhotic and non-cirrhotic HCC types involve differentially expressed miRNAs, which are correlated with distinctive pathological traits. To some extent, non-cirrhotic HCC seems more dependent on miRNA network regulation, but additional studies are needed to confirm this conclusion.

Identification of prognostic biomarkers of hepatocellular carcinoma via long noncoding RNA expression and copy number alterations

Epigenomics ◽  
2020 ◽  
Vol 12 (15) ◽  
pp. 1303-1315
Author(s):  
Weibo Du ◽  
Wenbiao Chen ◽  
Zheyue Shu ◽  
Dairong Xiang ◽  
Kefan Bi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Copy Number ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Prognostic Biomarkers ◽  
Copy Number Alterations ◽  
Sequencing Data ◽  
Cancer Genome Atlas

Aim: This study aimed to identify long noncoding RNAs (lncRNAs) with potential to be prognostic biomarkers of hepatocellular carcinoma (HCC) by analyzing copy number alterations (CNAs). Methods: RNA Sequencing data of 369 HCC patients was downloaded from The Cancer Genome Atlas database and analyzed with a series of systematic bioinformatics methods. Results: LncRNA-CNA association analysis revealed that many lncRNAs were located in sites frequently amplified or deleted. Three upregulated lncRNAs (LINC00689, SNHG20 and MAFG-AS1) with copy amplification and one downregulated lncRNA TMEM220-AS1 with copy deletion were associated with poor prognosis of HCC. Conclusion: This study reveals that differentially expressed lncRNAs correlate with CNAs in HCC. Moreover, the differentially expressed lncRNAs and their copy amplification/deletions could be promising prognostic biomarkers of HCC.

scholarly journals An lncRNA Model for Predicting the Prognosis of Hepatocellular Carcinoma Patients and ceRNA Mechanism

2021 ◽  
Vol 8 ◽  
Author(s):  
Hao Zhang ◽  
Renzheng Liu ◽  
Lin Sun ◽  
Xiao Hu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Rate ◽  
Liver Cancer ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
The Difference ◽  
Experimental Group

Liver cancer is a highly malignant tumor. Notably, recent studies have found that long non-coding RNAs (lncRNAs) play a prominent role in the prognosis of patients with liver cancer. Herein, we attempted to construct an lncRNA model to accurately predict the survival rate in liver cancer. Based on The Cancer Genome Atlas (TCGA) database, we first identified 1066 lncRNAs with differential expression. The patient data obtained from TCGA were divided into the experimental group and the verification group. According to the difference in lncRNAs, we used single-factor and multi-factor Cox regression to select the genes needed to build the model in the experimental group, which were verified in the verification group. The results showed that the model could accurately predict the survival rate of patients in the high and low risk groups. The reliability of the model was also confirmed by the area under the receiver operating characteristic curve. Our model is significantly correlated with different clinicopathological features. Finally, we built a ceRNA network based on lncRNAs, which was used to display miRNAs and mRNAs related to lncRNAs. In summary, we constructed an lncRNA model to predict the survival rate of patients with hepatocellular carcinoma.

scholarly journals Co-expression analysis and ceRNA network reveal eight novel potential lncRNA biomarkers in hepatocellular carcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8101
Author(s):  
Ren-chao Zou ◽  
Zhi-tian Shi ◽  
Shu-feng Xiao ◽  
Yang Ke ◽  
Hao-ran Tang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
Transcriptome Data ◽  
Cerna Network ◽  
Cancer Genome Atlas ◽  
Degree Of Malignancy

Background Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world, with a high degree of malignancy and recurrence. The influence of the ceRNA network in tumor on the biological function of liver cancer is very important, It has been reported that many lncRNA play a key role in liver cancer development. In our study, integrated data analysis revealed potential eight novel lncRNA biomarkers in hepatocellular carcinoma. Methods Transcriptome data and clinical data were downloaded from the The Cancer Genome Atlas (TCGA) data portal. Weighted gene co-expression network analysis was performed to identify the expression pattern of genes in liver cancer. Then, the ceRNA network was constructed using transcriptome data. Results The integrated analysis of miRNA and RNAseq in the database show eight novel lncRNAs that may be involved in important biological pathways, including TNM and disease development in liver cancer. We performed function enrichment analysis of mRNAs affected by these lncRNAs. Conclusions By identifying the ceRNA network and the lncRNAs that affect liver cancer, we showed that eight novel lncRNAs play an important role in the development and progress of liver cancer.

scholarly journals Integrating Transcriptomics for the Identification of Potential Age-related Genes and Cells in Three Major Urogenital Cancers Across the Cancer Genome Atlas

2020 ◽  
Author(s):  
Jinlong Cao ◽  
Jianpeng Li ◽  
Xin Yang ◽  
Pan Li ◽  
Zhiqiang Yao ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
R Package ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Age Related ◽  
Cancer Genome Atlas ◽  
Urogenital Cancers ◽  
Genome Atlas

Abstract Background: Cancer is often defined as a disease of aging. The majority of patients with urogenital cancers are the elderly, whose clinical characteristics are greatly affected by age and aging. Here, we aimed to explore age-related biological changes in three major urogenital cancers by integrative bioinformatics analysis.Methods: First, mRNA (count format) and clinical data for bladder cancer, prostate cancer and renal cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA) portal. The expressions of 64 cells were obtained by xCell deconvolution method. EdgeR package and limma package were used to analyze differentially expressed genes and cells in the young group and the old group, respectively. ClusterProfiler R package and clueGO plugin were used for enrichment analysis, and cytohubba plugin was used for hub genes analysis. Then co-expression analysis and chromosome distribution for hub genes were analyzed and demonstrated by RIdeogram R package. The clinical correlation of hub genes and key cells was analyzed by Graphpad Prism software. Finally, the correlation between hub genes and key cells was explored by corrplot R package.Results: We screened and identified 14 hub genes and 4 key cells related to age and urogenital cancers. The age-related differentially expressed genes and co-expressed genes were mainly enriched in muscle movement (Cl-, Ca2+), inflammatory response, antibacterial humoral immune response, substance metabolism and transport, redox reaction, etc. Most of the age-related genes are on chromosome 17. Moreover, the correlation between cells and genes was analyzed. Conclusion: Our study analyzed age-related genes and cells in the tumor microenvironment of urogenital cancers, and explored the pathways involved. This could contribute to personalized therapy for patients of different ages and a new understanding of the potential relationship between the aging microenvironment and urogenital cancers.

scholarly journals Differentially expressed liver exosome-related genes as a candidate prognostic biomarker for hepatocellular carcinoma

2020 ◽  
Author(s):  
Bangyou Zuo ◽  
Haitao Zhao ◽  
Jin Bian ◽  
Junyun Long ◽  
Xu Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
Cell Communication ◽  
High Risk Group ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed

Abstract Background The function of exosome includes cell-to-cell communication, neovascularization, and metastasis of cancer cell and drug resistance, which plays an important part in the occurrence and progression of hepatocellular carcinoma (HCC). Because the mechanism in this area is less studied, our goal is to identify exosome-related genes in HCC, establish a reliable prognostic model for liver cancer patients, and explore its underlying mechanisms. Methods The exoRbase database and The Cancer Genome Atlas (TCGA) database were used to analyze differentially expressed genes (DEGs). Cox regression and LASSO analysis were applied to determine DEGs closely related to overall survival (OS). Then the exosome-related prognostic model was constructed in TCGA and validated in the database of International Cancer Genome Consortium (ICGC). Nomogram graph was performed to predict the survival. CIBERSORT was used to estimate the score of different type of immune cells. DEGs related to immunotherapy are used to predict the effect of immunotherapy. Results 48 exosome-related DEGs were obtained and five genes (XPO1, IFI30, FBXO16, CALM1, MORC3) among them were selected to construct predictive model. Then we divided the HCC patients into low-risk and high-risk groups by the best cut-off value according to the X-tile software. The high-risk related to exosome were significantly associated with a poor prognosis. Moreover, the features related to exosome could positively regulate immune response. At the same time, the proportion of T cell regulatory factors (Tregs) and macrophages M2 is higher in the high-risk group, and high-risk group exhibited higher expression of immune checkpoint molecular including PD-L1, PD-L2, TIGIT, and IDO1. Conclusions Overall, our research showed that markers related to exosomes were potential biomarkers for the prognosis of HCC, providing an immunological perspective for the development of precision treatment.

scholarly journals Two immune-enhanced molecular subtypes differ in inflammation, immune checkpoints, mutations and outcome in Stage I-II colonic carcinoma.

2020 ◽  
Author(s):  
Dongxin Tang ◽  
Wei Huang ◽  
Zhu Yang ◽  
Xin Wu ◽  
Xianan Sang ◽  
...  
Keyword(s):  
Gene Mutations ◽  
The Cancer Genome Atlas ◽  
Colonic Carcinoma ◽  
Immune Checkpoints ◽  
Immune Gene ◽  
Immune Genes ◽  
Immune Gene Expression ◽  
New Ideas ◽  
Cancer Genome Atlas ◽  
C4 Subtype

Abstract Background: The purpose of this paper is to investigate the immune function of the tumor microenvironment and its clinical correlation with colonic carcinoma. Methods : Immune genes were downloaded from the The Cancer Genome Atlas （TCGA）database. Five subtypes are obtained by cluster screening based on immune gene expression data. Results: The C3 and C4 subtypes show stronger immune activity. In addition, the C4 subtype has the largest number of gene mutations and the worst prognosis. Most of the immune signatures are upregulated in the C4 subtype, while most of the immune infiltration-related cells are upregulated in the C3 and C4 subtypes. Conclusions: The different immune microenvironments between these subtypes may provide new ideas for immunotherapy strategies in colon carcinoma.

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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