scholarly journals Comprehensive Analysis of the Expression, Prognosis and Immune Infiltration of KPNA Family in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Xiangyi Chen ◽  
Dechen Yu ◽  
Hai-Yu Zhou ◽  
XiaoBo Zhang ◽  
Yicun Hu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Tumor Grade ◽  
Mapk Signaling ◽  
Clinicopathological Characteristics ◽  
Expression Level ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Patient Prognosis

Abstract Background: The primary function of the Karyophorin alpha family (KPNAs) is to assist the transport of proteins from the cytoplasm to the nucleus. Studies have found that KPNAs are involved in the occurrence and development of a variety of tumors. However, the expression level of KPNAs family members in HCC, its influence on prognosis, its relationship with immune infiltration, and its clinical significance are still unclear.Methods: We used UALCAN, GEPIA, HPA, TIMER, Kaplan-Meier Plotter, CBioPortal, String and Metascape databases to analyze the expression and mutation of KPNAs in Hepatocellular carcinoma (HCC), the expression level of KPNAs and the prognosis of patients, tumor immune cell infiltration, HCC clinicopathological characteristics Relationship. Finally, the biological functions of KPNAs related genes are analyzed. Results: The protein and mRNA of KPNAs were significantly up-regulated in HCC, and their expression levels were closely related to the prognosis of patients and the clinical characteristics of the tumor (tumor grade, stage, etc.). In addition, KPNAs in HCC are prone to mutations, which are not conducive to the prognosis of patients. Moreover, the expression of HCC is positively correlated with the infiltration of immune cells. Enrichment analysis found that KPNAs-related genes are mainly related to biological processes such as nuclear and cytoplasmic signaling, protein chromosome localization, and their pathways mainly include cell cycle and MAPK signaling pathways. Conclusion: KPNAs are significantly related to the occurrence, development and patient prognosis of HCC and may become the target of HCC immunotherapy in the future.

scholarly journals Identification and Validation of an 6-Metabolism-Related Gene Signature and Its Correlation With Immune Checkpoint in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
He Ren ◽  
Wanjing Li ◽  
Xin Liu ◽  
Shuliang Li ◽  
Hao Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Clinicopathological Characteristics ◽  
Gene Set Enrichment Analysis ◽  
Operating Characteristics ◽  
Kaplan Meier ◽  
Characteristics Analysis

Hepatocellular carcinoma (HCC) is a common malignant tumor with relatively high malignancy and rapid disease progression. Metabolism-related genes (MRGs) are involved in the pathogenesis of HCC. This study explored potential key MRGs and their effect on T-cell immune function in the tumor immune microenvironment to provide new insight for the treatment of HCC. Of 456 differentially expressed MRGs identified from TCGA database, 21 were screened by MCODE and cytoHubba algorithms. From the key module, GAD1, SPP1, WFS1, GOT2, EHHADH, and APOA1 were selected for validation. The six MRGs were closely correlated with survival outcomes and clinicopathological characteristics in HCC. Receiver operating characteristics analysis and Kaplan-Meier plots showed that these genes had good prognostic value for HCC. Gene set enrichment analysis of the six MRGs indicated that they were associated with HCC development. TIMER and GEPIA databases revealed that WFS1 was significantly positively correlated and EHHADH was negatively correlated with tumor immune cell infiltration and immune checkpoint expression. Finally, quantificational real-time polymerase chain reaction (qRT-PCR) confirmed the expression of WFS1 and EHHADH mRNA in our own patients’ cohort samples and four HCC cell lines. Collectively, the present study identified six potential MRG biomarkers associated with the prognosis and tumor immune infiltration of HCC, thus providing new insight into the pathogenesis and treatment of HCC.

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 SPP1 is a Prognostic Related Biomarker and Correlated With Tumor-Infiltrating Immune Cells in Ovarian Cancer

2021 ◽  
Author(s):  
Wen Gao ◽  
Sheng Yin ◽  
Haiyan Sun ◽  
Zhuyan Shao ◽  
Peipei Shi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Vital Role ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Secreted Phosphoprotein 1

Abstract Background: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of some cancer types, but little is known whether it is a bystander or an actual player on driving immune infiltration in ovarian cancer.Methods: In this study, the expression of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and SPP1 immumohistochemical staining analysis was assessed by The HPA database. The clinical outcomes between SPP1 expression and ovarian cancer patients were evaluated via Kaplan-Meier Plotter and PrognoScan dataset. Immune infiltration analyses were explored using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database.Results: SPP1 was found overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter OS and PFS survivals. Particularly, elevated SPP1 expression was significantly associated with stage III ovarian cancer. Notably, 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 ovarian cancer. Of particular importance, 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 ovarian cancer.Trial registration: Not applicable.

scholarly journals Upregulated CCNE1 Correlates with Poor Prognosis, Tumor Immune Infiltration and Escape in Breast Cancer

2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Cell ◽  
High Expression ◽  
Expression Level ◽  
Immune Cell Infiltration ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract Background Breast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.Methods At first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.Results The results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC. conclusions In summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.

scholarly journals Significance of HMMR Overexpression in Hepatocellular Carcinoma

2022 ◽  
Author(s):  
Weidong Zhao ◽  
Zhengxiang Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Progression ◽  
Enrichment Analysis ◽  
Progression Free Survival ◽  
Expression Level ◽  
Marker Genes ◽  
Surface Binding ◽  
Free Survival ◽  
Immune Infiltration ◽  
The Relationship

Abstract Background: Hyaluronan Mediated Motility Receptor (HMMR), as one of the key surface binding proteins of HA, is up-regulated in many tumors. What’s more, the expression level of HMMR is usually correlate with tumor progression and prognosis. However, the relationship between the expression of HMMR and the prognosis and immune infiltration of hepatocellular carcinoma (HCC) is still unclear.Methods: We analyzed the expression level of HMMR by TIMER database, GEO database and GEPIA database. The correlation between the HMMR expression and tumor prognosis was analyzed via the Kaplan-Meier plots. The TIMER database and GEPIA database were used to study the relationship between HMMR expression and immune infiltration. GO and KEGG enrichment analysis were used to explore the potential biological functions of HMMR.Results: HMMR expression was significantly higher in several human cancers, including HCC, than in corresponding normal tissues. High HMMR expression associated with poorer overall survival, disease-specific survival, progression-free survival and relapse-free survival in HCC patients. HMMR showed strong correlation with tumor-infiltrating B cells, CD4 + and CD8 + T cells, macrophages, neutrophils, and dendritic cells. Several immune marker genes expression, including CD86, IRF5, CD11b, KIRIDL4, CD11c, IFN-γ, STAT3, STAT5B, and CTLA4, have markedly positive correlations with HMMR expression. Enrichment analysis found that HMMR is mainly involved in cell cycle, DNA replication and repair, PLK1 pathway, E2F pathway, ATR pathway and AURORA B pathway.Conclusions: HMMR is a potential prognostic biomarker that influence tumor progression and correlated with tumor immune cells infiltration in HCC.

scholarly journals Bromine domain protein 4 is an important marker for prognosis of ovarian cancer and tumor immune infiltration

2021 ◽  
Author(s):  
Chujia Chen ◽  
Zhiyong Yang ◽  
Qiuchan Zhao ◽  
Bangming Xu ◽  
Donglin Cao
Keyword(s):  
Ovarian Cancer ◽  
Immune Cell ◽  
Expression Level ◽  
Immune Markers ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Domain Protein ◽  
Kaplan Meier Plotter

Abstract Background Ovarian cancer (OC) is one of the most common malignant gynecological tumors, but its pathogenesis is unclear. Bromine domain protein 4 (BRD4) is involved in the malignant transformation of cells, as well as the invasion and metastasis of tumor cells. The biological role of BRD4 in ovarian cancer is yet to be determined. Methods The differential expression of BRD4 in OC and corresponding normal tissues was evaluated by exploring the Tumor Immune Assessment Resources (TIMER) and the Oncomine database. The correlation between the expression level of BRD4 and the prognosis of OC patients was evaluated using the Kaplan-Meier Plotter database. Using TIMER, we further studied the correlation between BRD4 and tumor immune cell infiltration. Results The expression of BRD4 was significantly higher in patients with OC, and high BRD4 expression was closely related to low overall survival rate. The BRD4 expression was associated with the levels of immune markers of macrophages, dendritic cells, neutrophils, and various effector T cells. Taken together, these findings show that BRD4 expression is significantly related to immune infiltration in OC and suggest that BRD4 might play an important role in the immune evasion of OC cells. Conclusion The expression level of BRD4 in OC tissues is significantly upregulated, and its high expression is significantly associated with poor prognosis of patients and is closely related to tumor immune infiltration. These results suggest that BRD4 can be used as a prognostic marker and a marker of immune infiltration in OC.

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 Upregulated CCNE1 Correlates with Poor Prognosis, Tumor Immune Infiltration and Escape in Breast Cancer

2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Cell ◽  
High Expression ◽  
Expression Level ◽  
Immune Cell Infiltration ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract BackgroundBreast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.MethodsAt first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.ResultsThe results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC.ConclusionIn summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.

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 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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