scholarly journals Erythropoietin as a Potential Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Huange Zhu ◽  
Yanping Zhang ◽  
Jiafeng Yin ◽  
Jie Lu ◽  
Hailong Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Patient Survival ◽  
Prognostic Biomarker ◽  
Immune Cell Infiltration ◽  
Checkpoint Gene ◽  
Immune Infiltration ◽  
Cancer Types

Abstract Background. Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis. Immune checkpoint genes are considered novel tumor immunotherapy targets for many cancer types. Erythropoietin (EPO) is a protein secreted mainly in the liver and kidneys; in several cancer types, EPO expression stimulates tumor growth and corelates with patient survival. The study aimed to identify EPO as a prognostic biomarker correlated with immune infiltration in HCC. Methods. We investigated the correlation between EPO expression and HCC patient clinical characteristics using data from The Cancer Genome Atlas. The relationship between EPO expression and HCC patient survival was investigated using Kaplan–Meier analysis. We also used R (v.3.6.3) to analyze the correlation between EPO expression and immune infiltration in HCC. Results. We found that EPO expression was downregulated in HCC. Notably, EPO was upregulated in advanced-stage HCC and had a diagnostic value of 0.83 (p < 0.001) in HCC diagnosis. HCC patients with increased EPO expression had poor prognoses. Furthermore, altered EPO expression was associated with immune cell infiltration and immune checkpoint gene expression in HCC. Conclusions. EPO expression was positively correlated with hepatocellular carcinoma stage, and negatively correlated with patient prognosis, with influening HCC immune cell infiltration and checkpoint gene expression. EPO can be as both a potential prognostic biomarker and a novel potential treatment target for HCC.Our work is not a clinical trial, but preclinical basic study.

scholarly journals Signature Based on Immune-Related LncRNA Can Predict Overall Survival of Osteosarcoma Patients

2020 ◽  
Author(s):  
Longqing Li ◽  
Lianghao Zhang ◽  
Manhas Adbul Khader ◽  
Yan Zhang ◽  
Xinchang Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
High Throughput Sequencing ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Low Risk ◽  
Checkpoint Gene ◽  
Cox Regression Analysis

Abstract Background: Osteosarcoma is a malignant bone tumor common in children and adolescents. Metastatic status remains the most important guideline for classifying patients and making clinical decisions. Despite many efforts, newly diagnosed patients receive the same therapy that patients have received over the last 4 decades. With the development of high-throughput sequencing technology and the rise of immunotherapy, it is necessary to deeply explore the immune molecular mechanism of osteosarcoma.Methods: We obtained RNA-seq data and clinical information of osteosarcoma patients from TCGA database and TARGET database. With the help of co-expression analysis we identified immune-related lncRNA and then by means of univariate Cox regression analysis prognostic-related lncRNA was screened out. And also by using least absolute shrinkage and selection operator regression method a model based on immune-related lncRNA was constructed. The differences in overall survival, immune infiltration, immune checkpoint gene expression, and tumor microenvironmental immunity type between the two groups were evaluated.Results: We constructed a signature consisting of 13 lncRNA. Our results show that signatures can reliably predict the overall survival of patients with osteosarcoma and can bring net clinical benefits. Further more, the signatures can be used for further risk stratification of the metastasis patients. Patients in the low-risk group had higher immune cell infiltration and immune checkpoint gene expression. The results from gene set variation analysis show that patients in low-risk group are closely related to immune-related pathways when compared with patients in high-risk group. Finally, patients in the low-risk group are more likely to be classified as TMIT I and hence more likely to benefit from immunotherapy.Conclusion: Our signature may be a reliable marker for predicting the overall survival of patients with osteosarcoma.

scholarly journals YAP1 is a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Pancreatic Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Kai Sun ◽  
Xue-de Zhang ◽  
Xiao-yang Liu ◽  
Pei Lu
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Prognostic Value ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Long Term Outcome

Yes-associated protein-1 (YAP1) is an important effector of the Hippo pathway and has crosstalk with other cancer signaling pathways. It induces an immunosuppressive tumor microenvironment by activating pathways in several cellular components. However, the mechanisms by which it drives immune infiltration in pancreatic cancer remain poorly understood. We analyzed the expression of YAP1 as well as its prognostic value and correlations with immune infiltrates in various cancers, with a focus on pancreatic cancer. In particular, using the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA) database, we found that YAP1 is differentially expressed between tumor tissues and control tissues in a number of cancers and in particular, is elevated in pancreatic cancer. Using the Kaplan–Meier plotter, GEPIA, and Long-term Outcome and Gene Expression Profiling database of pan-cancers (LOGpc), we further established the prognostic value of YAP1. We found that YAP1 expression was significantly related to outcomes in multiple types of cancer based on data from The Cancer Genome Atlas, particularly in pancreatic cancer. Correlations between YAP1 and immune cell infiltration and immune cell marker expression were examined using Tumor Immune Estimation Resource and GEPIA. High expression levels of YAP1 were significantly associated with a variety of immune markers and immune cell subsets in pancreatic cancer. These results suggest that YAP1 is correlated with patient outcomes and tumor immune cell infiltration in multiple cancer types and is a valuable prognostic biomarker in pancreatic cancer.

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 SNHG3/miR-148a-3p Axis–mediated High Expression of DNMT1 Correlates with Poor Prognosis and Tumor Immune Infiltration of Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Ninghua Yao ◽  
Wei Jiang ◽  
Jie Sun ◽  
Chen Yang ◽  
Wenjie Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Immune Cell Infiltration ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Immune Infiltration ◽  
Computer Analyses ◽  
Dnmt1 Expression

Abstract Background Epigenetic reprogramming plays an important role in the occurrence, development, and prognosis of hepatocellular carcinoma (HCC). DNA methylation is a key epigenetic regulatory mechanism, and DNA methyltransferase 1 (DNMT1) is the major enzyme responsible for maintenance methylation. Nevertheless, the role and mechanism of DNMT1 in HCC remains poorly defined. Methods In the current study, we conducted pan-cancer analysis for DNMT1’s expression and prognosis using The Cancer Genome Atlas (TCGA) data set. We conducted gene Set Enrichment Analysis (GSEA) between high-and-low DNMT1 expression groups to identify DNMT1-related functional significance. We also investigated the relationship between DNMT1 expression and tumor immune microenvironment, including immune cell infiltration and the expression of immune checkpoints. Through a combination series of computer analyses (including expression analyses, correlation analyses, and survival analyses), the noncoding RNAs (ncRNAs) that contribute to the overexpression of DNMT1 were ultimately identified. Results We found that DNMT1 was upregulated in 16 types of human carcinoma including HCC, and DNMT1 might be a biomarker predicting unfavorable prognosis in HCC patients. DNMT1 mRNA expression was statistically associated with age, histological grade, and the level of serum AFP. Moreover, DNMT1 level was significantly and positively linked to tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. Meanwhile, Gene Set Enrichment Analysis (GSEA) revealed that high-DNMT1 expression was associated with epithelial mesenchymal transition (EMT), E2F target, G2M checkpoint, and inflammatory response. Finally, through a combination series of computer analyses the SNHG3/hsa-miR-148a-3p/DNMT1 axis was confirmed as the potential regulatory pathway in HCC. Conclusion SNHG3/miR-148a-3p axis upregulation of DNMT1 may be related to poor outcome, tumor immune infiltration, and regulated malignant properties in HCC.

scholarly journals Immune Implication of ASF1B Gene in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Tao Meng ◽  
Zhong Tong ◽  
Ming-Ya Yang ◽  
Jing-Jing Wang ◽  
Li-Xin Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Risk Score ◽  
Immune Cell ◽  
Risk Group ◽  
External Validation ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Test Set

Abstract Background: Anti-silencing function 1B (ASF1B) has been demonstrated to contribute to tumorigenesis. However, its carcinogenic and immune effects in hepatocellular carcinoma (HCC) have not been reported. This study aimed to identify immune role of ASF1B in HCC.Methods: HCC datasets obtained from The Cancer Genome Atlas (TCGA) database were used to investigate the role of ASF1B gene in HCC, followed by validation using Gene Expression Omnibus (GEO) datasets and Gene Expression Profiling Interactive Analysis (GEPIA) website. CIBERSORT analysis was performed to evaluate immune cell infiltration levels. The TISIDB and cBioPortal network tool were used to seek ASF1B-associated immunomodulators and its co-expressed genes. TCGA cohort was divided into train set and test set according to the ratio of 7:3. Cox regression was used to identify ASF1B-associated prognostic immunomodulators in train set, followed by internal validation using the test set. Based on the median risk-score, HCC patients were divided into high- and low-risk group for the further survival curves and receiver operating characteristic (ROC) analysis, as well as nomogram and calibration curves analysis. Finally, the dataset collected from the GEO was adopted for external validation.Results: ASF1B was over-expressed in TCGA HCC cohort and contributed poor prognosis, which was verified in two GEO datasets (GSE14520 and GSE6764) and GEPIA, as well as Kaplan Meier Plotter network tool. The immune cell infiltration levels were found to be associated with the ASF1B copy numbers and mRNA expression. A total of 78 ASF1B-associated genes were screened out, including 7 immunoinhibitors, 21 immunostimulators and 50 tightly co-expressed genes. Finally, 5 ASF1B-associated genes (TNFSF4, TNFRSF4, KDR, MICB and CST7) were identified to be strongly related to HCC survival. Survival analysis demonstrated that the prognosis of patients in high-risk group was poor. The prognosis predict model, which was established by nomogram based on risk-score, and was validated in both TCGA test set and GEO validated datasets, exerted excellent predictive power in this study.Conclusion: Our findings showed that the ASF1B was associated with HCC immunity. The selected ASF1B-asociated immune markers could be promising biomarkers for the prognosis of HCC.

scholarly journals Identification of Crucial Methylation Genes Associated With Immune Cell Infiltration in Twin-to-twin Transfusion Syndrome Using Co-methylation Analysis

2021 ◽  
Author(s):  
Chuang Li ◽  
Yuan Wang ◽  
Caixia Liu ◽  
Shaowei Yin
Keyword(s):  
Gene Expression ◽  
Immune Cell ◽  
Interaction Network ◽  
Cell Infiltration ◽  
Future Research ◽  
Regulation Mechanism ◽  
Immune Cell Infiltration ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Neurodevelopmental Abnormalities

Abstract Background: DNA methylation (DNAm), is an important transcriptional regulation mechanism, relevant to various diseases. Twin-to-twin transfusion syndrome (TTTS) is a complication in twin pregnancies resulting from disproportionate blood circulation. Survivors of TTTS show a high risk of neurodevelopmental abnormalities, particularly in the hippocampus, which is important in learning and memory. Here, we investigate gene expression and DNAm in hippocampus tissues of TTTS specimens. Methods: DNAm and gene expression levels were compared among the three groups: 10 recipients, 10 donors, and 10 matched control, using methylation microarray. We further explored the immune infiltration of six immune cell sub-populations using EpiDISH analysis. The methylated sites related to immune cell infiltration were identified using the WGCNA package. We explored the core methylation genes in the protein-protein interaction network using the MCODE plugin in Cytoscape software. Results: There were 188 differential methylation sites among three groups. Based on WGCNA, we found that the turquoise module containing 174 CpG sites is significantly related to the immune infiltration level. And four hub genes correlated with immune infiltration level, namely, PTPRJ, FYN, LYN, and AKT1, and were identified using gene sub-network analysis. Conclusions: We identify the four hub methylation genes related to immune infiltration in the TTTS. The molecular function of hub genes is still explored in the future research.

scholarly journals Nuf2 Is a Prognostic-Related Biomarker and Correlated With Immune Infiltrates in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xingwei Xie ◽  
Shanshan Jiang ◽  
Xiang Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Free Survival ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Immune Biomarkers ◽  
And Function

Nuf2 participates in the regulation of cell apoptosis and proliferation by regulating the binding of centromere and spindle microtubules to achieve the correct separation of chromosomes. Previous reports have suggested that Nuf2 may play a role in various human cancers. However, the mechanism and function of Nuf2 in the development of Hepatocellular carcinoma (HCC) remains uncertain. This study investigated the prognostic potential of Nuf2 and its relation with immune cell infiltration in HCC. Nuf2 expression in tumor cells was examined using the TIMER and Oncomine databases, and its prognostic potential was assessed via the Kaplan-Meier plotter and GEPIA databases. The relationships between Nuf2 and tumor immune infiltration were analyzed using TIMER. The relationships between Nuf2 and biomarkers of tumor immune infiltration were analyzed using TIMER and GEPIA. Here we revealed that Nuf2 expression increased in tumor tissues containing HCC, and this correlated with poor relapse-free survival, disease-specific survival, progression-free survival, and overall survival in patients with HCC regardless of grades, genders, races, drinking behaviors and other clinical factors. Additionally, high expression of Nuf2 was positively correlated with differential immune cell infiltration and various immune biomarkers. Our work demonstrated that Nuf2 could be a potential prognostic biomarker and could be related to tumor immune cell infiltration in HCC.

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