scholarly journals CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhihuai Wang ◽  
Shuai Chen ◽  
Gaochao Wang ◽  
Sun Li ◽  
Xihu Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Disease Free Survival ◽  
In Silico Analysis ◽  
Gene Markers ◽  
Free Survival ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Tumor Tissues

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

LTBP2 Serves as a Prognostic Biomarker and Correlated with the Immune Infiltration in Stomach and Colon Cancer

2021 ◽  
Author(s):  
Shuai Chen ◽  
Zhihuai Wang ◽  
Yu Gong ◽  
Hanyang Liu ◽  
Haojun Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Colon Adenocarcinoma ◽  
Progression Free Survival ◽  
Transforming Growth Factor Β ◽  
Gene Markers ◽  
Free Survival

Abstract Latent transforming growth factor β binding protein 2 (LTBP2) involved in the TGF pathway to induce immunosuppression and immune response. However, the association between the outcome of patients, the infiltrating immune cell and LTBP2 expression is still unclear in human cancers. The LTBP2 expression was analyzed by TIIMER and Oncomine database. Based on the Prognoscan database, the GEPIA database, and the Kaplan-Meier plotter database, the prognostic value was assessed. The immune and stromal score of tumors was calculated through ESTIMATE. We additionally explore the relationship among the LTBP2 expression, the infiltrating immune cells, and its gene markers in the TIMER, TISIDB, and GEPIA database, the enriched KEGG pathways of LTBP2 were evaluated by GSEA. The result showed that LTBP2 expressed differently among the normal and tumor tissues in various sorts of cancer involving stomach adenocarcinoma (STAD) and colon adenocarcinoma (COAD), and three cohorts of COAD presented that the LTBP2 high expression was linked with poorer disease-free survival and the elevated LTBP2 expression correlated with progression-free survival and poorer overall survival in STAD. The LTBP2 was correlated with the stromal and immune score in different cancers. The infiltrating immune cells include the CD8+T cells and CD4+T cells, macrophages, neutrophils, and dendritic cells were correlated with the LTBP2 expression. Meanwhile, LTBP2 was related to the infiltrating immune cell’s gene markers and enriched immune-related pathways in STAD and COAD. LTBP2 was the potential to be an independent predictor for the prognosis and a new target for immunotherapy in STAD and COAD.

scholarly journals The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12123
Author(s):  
Bi Peng ◽  
Yuanliang Yan ◽  
Zhijie Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Metal Ion ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Expression Levels ◽  
Normal Tissues ◽  
Molecular Profiles

Background Serving as N6-methyladenosine demethylases, the AlkB family is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the molecular profiles and clinical values of the AlkB family in HCC are not well known. Methods Several bioinformatics tools and in vitro experiments were used to identify the immune-related profiles and prognostic values of AlkB family in HCC. Results In this study expression levels of ALKBH1/2/3/4/7 were all remarkably increased in HCC tissues when compared with normal tissues. Quantitative PCR (qPCR) and immunohistochemistry were used to validate the expression of AlkB family members in HCC tissues and normal liver tissues. In addition, high expression levels of ALKBH4 were negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients with HCC. Increased ALKBH4 was also associated with pathological stage in HCC patients. The molecular profiles of AlkB family in HCC were mainly associated with peptidyl-serine modification, peptidyl-tyrosine modification, regulation of metal ion transport, etc. Furthermore, tumor-infiltrating immune cell analysis indicated that ALKBH1/2/3/4/5/6/7/8 and FTO were related to the infiltration of different immune cell, such as CD8+ T cells, macrophages, neutrophils, dendritic cells and CD4+ T cells. We also discovered that the methylation levels of ALKBH1/2/4/5/6/8 and FTO were remarkably reduced in HCC tissues. Conclusions Collectively, our findings may deepen the understanding of specific molecular profiles of the AlkB family in HCC pathology. In particular, ALKBH4 could serve as a promising prognostic candidate for treating HCC, and these results might potentiate the development of more reliable therapeutic strategies for patients with HCC.

scholarly journals ABL1 Is a Prognostic Marker and Associated with Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Rongqiang Liu ◽  
Weihao Kong ◽  
ZeKun Jiang ◽  
Shiyang Zheng ◽  
Xiaofeng Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Neurological Diseases ◽  
Disease Free Survival ◽  
Protein Translation ◽  
Mitochondrial Activity ◽  
Nonalcoholic Fatty Liver ◽  
Immune Infiltration

Background. The role of ABL1 in hepatocellular carcinoma (HCC) is still unclear. Therefore, this study aims to explore the potential role of ABL1 in the progression of HCC using bioinformatics methods. Methods. We analyzed the expression, prognostic potential, and immune cell effect of ABL1 in HCC by using a variety of datasets. Results. ABL1 is highly expressed in HCC and associated with unfavorable overall survival (OS) and disease-free survival (DFS). Functional network analysis revealed that ABL1 plays an important role in mitochondrial activity, ATP metabolism, protein translation and metabolism, various neurological diseases, nonalcoholic fatty liver disease, and notch signaling pathway. In addition, we found that ABL1 expression was closely correlated with B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells. Furthermore, ABL1 expression was positively associated with the expression levels of immune checkpoint genes, such as PD-1L, TIM3, TIGIT, and CTLA4. Conclusion. ABL1 is associated with immune infiltration and prognosis of HCC.

scholarly journals Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Pan ◽  
Geng-yuan Hu ◽  
Shi Jiang ◽  
Shun-jie Xia ◽  
Hendi Maher ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Aerobic Glycolysis ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Sorafenib Therapy ◽  
Tumor Tissues ◽  
Cancer Genome Atlas ◽  
Advanced Stages ◽  
Disease Free

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

scholarly journals CDKN2A is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Jun-peng Luo ◽  
Jing Wang ◽  
Jin-hua Huang
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Immune Cell ◽  
Kinase Inhibitor ◽  
Prognostic Biomarker ◽  
Disease Free Survival ◽  
Cyclin Dependent Kinase ◽  
Strong Correlations ◽  
Immune Infiltration ◽  
Cyclin Dependent Kinase Inhibitor

Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) is an essential regulator of immune cell functionality, but the mechanisms whereby it drives immune infiltration in hepatocellular carcinoma (HCC) remain unclear. In the current study, we studied the association with CDKN2A expression and immune invasion with the risk of developing HCC. A totally of 2207 different genes were found between HCC and adjacent liver tissues from TCGA and GEO databases. CDKN2A was highly expressed in HCC and associated with poorer overall survival and disease-free survival. Notably, CDKN2A expression was positively correlated with infiltrating levels into purity, B cell, CD+8 T cell, CD+4 T cell, macrophage, neutrophil, and dendritic cells in HCC. CDKN2A expression showed strong correlations between diverse immune marker sets in HCC. These findings suggest that CDKN2A expression potentially contributes to regulation of tumor-associated macrophages and can be used as a prognostic biomarker for determining prognosis and immune infiltration in HCC.

scholarly journals HULC and H19 Played Different Roles in Overall and Disease-Free Survival from Hepatocellular Carcinoma after Curative Hepatectomy: A Preliminary Analysis from Gene Expression Omnibus

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Zongguo Yang ◽  
Yunfei Lu ◽  
Qingnian Xu ◽  
Bozong Tang ◽  
Cheol-Keun Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Vascular Invasion ◽  
Disease Free Survival ◽  
Gene Expression Omnibus ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Tumor Tissues ◽  
Disease Free

Objective. This study aimed to evaluate the relationships between long noncoding RNAs (lncRNAs) in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and survival.Methods. We correlated the lncRNAs in tumor tissues with HCC survival and clinicopathological features based on Gene Expression Omnibus expression profile GSE36376.Results. Eight lncRNAs and 240 HCC patients were included. Cox regression analysis indicated that HULC was a positive factor for HCC overall survival (HR = 0.885, 95% CI = 0.797–0.983, andP=0.023) and disease-free survival time (HR = 0.913, 95% CI = 0.835–0.998, andP=0.045). H19 and UCA1 were both demonstrated to be risk factors of HCC disease-free survival in multivariate Cox model (HR = 1.071, 95% CI = 1.01–1.137, andP=0.022and HR = 2.4, 95% CI = 1.092–5.273, andP=0.029, resp.). But Kaplan-Meier method showed no significant association between UCA1 and HCC disease-free survival (log rankP=0.616). Logistic regression demonstrated that H19 was overexpressed in HBV-infected patients (OR = 1.14, 95% CI = 1.008–1.29, andP=0.037). HULC had a significant association with vascular invasion (OR = 0.648, 95% CI = 0.523–0.803, andP<0.001). H19 and MEG3 were both considered to be risk factors for high AFP level (OR = 1.45, 95% CI = 1.277–1.646, andP<0.001and OR = 1.613, 95% CI = 1.1–2.365, andP=0.014, resp.).Conclusions. Contributing to decreased susceptibility to vascular invasion, upregulation of HULC in tumor tissues was positively associated with HCC survival. In contrast, H19 overexpression might be risk factor for HCC aggressiveness and poor outcomes.

scholarly journals Positive Immuno-Modulation Following Radiofrequency Assisted Liver Resection in Hepatocellular Carcinoma

2019 ◽  
Vol 8 (3) ◽  
pp. 385 ◽  
Author(s):  
Kai Wen Huang ◽  
Kumar Jayant ◽  
Po-Huang Lee ◽  
Po-chih Yang ◽  
Chih-Yang Hsiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Liver Resection ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Treg Cells ◽  
Chi Square ◽  
Immunological Parameters ◽  
Exact Test ◽  
Liver Resections

Introduction: Hepatocellular carcinoma (HCC) often develops on a background of chronic inflammation and a complex immunosuppressive network with increased regulatory T cells, impaired CD8+ T cells and the secretion of immunosuppressive cytokines. Previous clinical studies have reported a superior disease-free survival (DFS) following a radiofrequency-based ablation or resection in HCC tumours compared to conventional liver resection techniques. The aim of this study was to investigate whether there is any correlation with the use of a radiofrequency-assisted liver resection and clinical outcome. Material and Methods: Patients’ peripheral blood was collected prior and 7 days following surgery from patients undergoing a liver resection for HCC. There were 5 liver resections performed using CUSA and 6 liver resections with the RF-based device, HabibTM 4X. The primary endpoint of the study was to assess the immunological parameters of circulating immune cell populations as well as serum cytokines. The Student’s t-test, chi-square or Fisher’s Exact test were applied for statistical comparisons, as appropriate. Results: Patients undergoing an RF-assisted liver resection with HabibTM 4X had a significant decrease in the inhibitory Treg cells (p = 0.002) and a significant increase in CD8+ T lymphocytes (p = 0.050) and CD4+CD45RO+/CD4+ memory T cells (p = 0.002) compared to those patients undergoing a liver resection with CUSA. It was also noted that the RF-assisted liver resection group had a significant decrease in circulating TGF-ß (p = 0.000), IL10 (p = 0.000) and a significant increase in IFN-gamma (p = 0. 027) and IL-17 compared to the CUSA group. Conclusion: A liver resection with RF-based device HabibTM 4X was associated with positive immunomodulatory changes in circulating immune cells and circulating cytokines which could explain the significant improvement in DFS.

scholarly journals The Expression of LIMK1 is Related to the Poor Prognosis and Immune Function of Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Yisheng Peng ◽  
Jun Fan ◽  
Gang Zhu ◽  
Shunde Tan ◽  
Jianfei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Function ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Tnm Staging ◽  
Immune Infiltration ◽  
Protein Protein Interaction ◽  
Normal Tissues ◽  
The Poor ◽  
Kaplan Meier

Abstract Background: According to reports, LIMK1 may have the effect of promoting tumor progression. However, the effect of the expression of LIMK1 on the healing of patients with hepatocellular carcinoma and its effect on the immune function are still not clear. Therefore, we analyzed the effect of LIMK1 on the healing of patients with hepatocellular carcinoma and its correlation with immunity through bioinformatics analysis.Methods: Download the transcriptional expression profile of LIMK1 in hepatocellular carcinoma tissues and normal tissues in TCGA, and study its expression in hepatocellular carcinoma. Study the expression of LIMK1 in hepatocellular carcinoma through CPTAC and HPA database. The Kaplan-Meier method was used to evaluate the effect of LIMK1 expression on the survival of patients with hepatocellular carcinoma. Use the STRING database to construct a protein-protein interaction (PPI) network. Use the "ClusterProfiler" package for feature-rich analysis. Use TISIDB database and Xiantao platform to study the relationship between LIMK1 mRNA expression and immune infiltration.Results: The expression of LIMK1 in hepatocellular carcinoma tissues was significantly up-regulated. Increased expression of LIMK1 mRNA is related to high TNM staging. In the ROC curve, when the cut-off level is 1.813, the sensitivity and specificity of LIMK1 to distinguish hepatocellular carcinoma from adjacent controls are 80.7% and 86%, respectively.The Kaplan-Meier curve shows that the higher the expression of LIMK1, the worse the survival of patients with hepatocellular carcinoma (42.2 months vs. 70 months, P = 0.001). Correlation analysis studies have shown that the expression of LIMK1 mRNA in hepatocellular carcinoma is related to immune cell infiltration.Conclusion: Up-regulation of LIMK1 may affect the survival rate and immune invasion of hepatocellular carcinoma. Studies have shown that LIMK1 may be related to the poor prognosis of hepatocellular carcinoma, and has a certain relationship with the immune infiltration of hepatocellular carcinoma.

scholarly journals SPP1 is a Prognostic Related Biomarker and Correlated with Tumor-Infiltrating Immune Cells in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Xiaofeng Wang ◽  
Kun Zhang ◽  
Li Geng ◽  
DongLi Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Tumor Promoter ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Secreted Phosphoprotein 1

Abstract Background: Secreted phosphoprotein 1 (SPP1) functions as a tumor promoter in varies tumors, but little is known whether it is an actual player on driving immune infiltration in hepatocellular carcinoma. Methods: In this study, we identified the expression of SPP1 by Oncomine, GEPIA and TIMER databases, and assessed SPP1 immumohistochemical staining analysis by The HPA database. We evaluated the clinical outcomes between SPP1 expression and hepatocellular carcinoma patients via Kaplan-Meier Plotter. We also tested the relationship between SPP1 and critical oncogenes by TIMER and GEPIA databases. Then we explored immune infiltration analyses using TIMER and TISIDB datasets. In addition, we performed functional enrichment analyses with Metascape and GeneMANIA databases. Results: We found that SPP1 overexpressed in hepatocellular carcinoma tissues and high SPP1 expression was correlated with shorter OS and PFS survivals in hepatocellular carcinoma patients. SPP1 expression is positive correlation with critical oncogenes related stemness associated genes, cell cycle and proliferation, therapeutic resistance, metastasis, and tumor angiogenesis in hepatocellular carcinoma. Importantly, SPP1 expression was positively correlated with infiltrating levels of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression showed strong correlations with diverse immune hallmark sets in hepatocellular carcinoma. Notably, functional enrichment analysis suggested that SPP1 strong related with immune response. Conclusions: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in hepatocellular carcinoma.

scholarly journals Prognosis and Immune Infiltration of Chromobox Family Genes in Sarcoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Jian Zhou ◽  
Ziyuan Chen ◽  
Ming Zou ◽  
Rongjun Wan ◽  
Tong Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Line ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Sarcoma Cell ◽  
Free Survival ◽  
Sarcoma Cell Line ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Human Sarcoma

BackgroundChromobox family genes (CBXs) are known to play roles in numerous modifications of the chromatin in order to inhibit the transcription of target genes. CBXs have been shown to be expressed at high levels in many types of cancer and can also serve as a target gene for therapeutic purposes. However, little is known about the expression and prognostic value of CBXs in human sarcomas.MethodsThe transcription level of CBXs was analyzed using the Oncomine dataset, and the differential expression of CBXs in sarcoma was reported by the Gene Expression Profiling Interactive Analysis (GEPIA) dataset. We also used the CCLE dataset to evaluate the expression of CBXs in a sarcoma cell line. The prognostic value of CBXs was analyzed using GEPIA and Kaplan–Meier analysis. In addition, the corrections between CBXs and their co-expressed genes were reported using Oncomine and GEPIA datasets. DAVID was used to perform GO function enrichment analysis for the CBXs and their co-expression genes. Finally, TIMER was used to analyze the immune cell infiltration of CBXs in patients with sarcoma.ResultsHP1-α/β/γ (CBX1/3/5) and CBX4/6/8 were found to be overexpressed in human sarcoma, and CBXs were upregulated in almost all the sarcoma cell line. The expression levels of HP1-α/β/γ (CBX1/3/5) and CBX7 were associated with overall survival (OS) in patients with sarcoma, while high expression levels of CBX7 were related to disease-free survival (DFS). In addition, the expression levels of CBX2/6/7 were related to recurrence-free survival (RFS). We also found that the CBX family was positively correlated with the infiltration of immune cells, including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells, in sarcoma.ConclusionsThe results from the present study indicated that CBXs were significantly associated with prognosis and immunological status in sarcoma. These data suggest that CBXs could serve as potential biomarkers for prognosis and immune infiltration in human sarcoma.

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