scholarly journals Comprehensive Analysis of Prognostic Value and Immune Infiltration of the NT5DC Family in Hepatocellular Carcinoma

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Rongqi Li ◽  
Rongqiang Liu ◽  
Shiyang Zheng ◽  
Wenbin Liu ◽  
Hui Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Prognostic Value ◽  
Biological Function ◽  
Malignant Tumors ◽  
Family Members ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Metabolic Process ◽  
Poor Overall Survival

Background. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its incidence is obviously increasing. The NT5DC family has been shown to be involved in the progression of many tumors. However, the biological function of NT5DC family members in HCC is still not well understood. Methods. Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, GeneMANIA, Metascape, and TIMER were applied to assess the biological function of NT5DC family members in HCC. Results. Most of the NT5DC family members were highly expressed in HCC. High expression of NT5C2, NT5DC2, and NT5DC3 was closely associated with higher tumor stage and poor overall survival (OS). In addition, high NT5DC2 and NT5DC3 expression also predicted poor disease-free survival (DFS). Enrichment analysis revealed that the NT5DC family in HCC mainly involved the IMP metabolic process, purine ribonucleoside monophosphate metabolic process, and purine nucleoside monophosphate metabolic process. The expression of NT5DC family members was closely related to the infiltration of some immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusion. Our findings provided new insights into the biological function and prognostic value of NT5DC family members in HCC.

scholarly journals Combining Bioinformatics and Experiments to Identify and Verify Gene Prognostic Markers in Hepatocellular Carcinoma

2021 ◽  
pp. 1-12
Author(s):  
Li Luo ◽  
Rong Wang ◽  
Liaoyun Zhang ◽  
Piao Zhang ◽  
Dongmei Tian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes

Background: Hepatocellular Carcinoma (HCC) is one of the highly malignant tumors threatening human health. The current research aimed to identify potential prognostic gene biomarkers for HCC. Materials and Methods: Microarray data of gene expression profiles of HCC from GEO were downloaded. After screening overlapping differentially expressed genes (DEGs) by R software. The STRING database and Cytoscape were used to identify hub genes. Cox proportional hazards regression was performed to screen the potential prognostic genes. Moreover, quantitative real-time PCR analyses were performed to detect the expression of ANLN in liver cancer cells and tissues. Finally, its possible pathways and functions were predicted using gene set enrichment analysis (GSEA). Result: A total of 566 DEGs were obtained from the overlapping analysis of three mRNA microarray dataset. Six key hub genes including RACGAP1, KIF20, DLGAP5, CDK1, BUB1B and ANLN, were associated with poor prognosis of patients with HCC. Higher expression of ANLN was associated with reduced overall survival and disease-free survival in patients with HCC. Multivariate analysis revealed that ANLN expression was an independent risk factor affecting overall survival. RT-PCR and Western blot analysis further demonstrated that ANLN expression was increased in HCC compared with patient-matched adjacent normal tissues. Notably, Gene enrichment analysis revealed that DEGs in ANLN-high patients were enriched in cell cycle, DNA duplication and p53 signaling pathway. Conclusion: The high expression of RACGAP1, KIF20, DLGAP5, CDK1, BUB1B and ANLN might be poor prognostic biomarkers in HCC patients, and may help to individualize the management of HCC.

scholarly journals Comprehensive Analysis of the Expression, Prognostic Value and Correlations with Immune Infiltration of PBX Family Members in Colorectal Cancer

2021 ◽  
Author(s):  
Yanping Hu ◽  
Yihang Shen
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Interaction Analysis ◽  
Family Members ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Immune Infiltration ◽  
Colorectal Cancer Patients

Abstract Background: Colorectal cancer is the third commonest cancer and the second leading cause of cancer deaths globally. The Pre-B-cell leukemia transcription factor (PBX) family plays an essential biological role in the growth and development of the organism. PBX genes have been found to be implicated in the tumorigenesis of a variety of human tumors through multiple pathways, but its function in colorectal cancer is unclear. Methods: The expression pattern, prognostic value and relationship with immune infiltration of PBX genes in patients with colorectal cancer were investigated using the Oncomine, GEPIA, Kaplan-Meier Plotter and TIMER databases. In addition, gene mutation and interaction analysis of PBX family members in colorectal cancer patients using cBioPortal and GeneMANIA databases, respectively.Results: We revealed that a significantly lower expression level of PBX1, PBX2 and PBX3 in colorectal cancer tissues than in normal tissues, and the expression levels of PBX1 and PBX2 were significantly correlated with clinical tumor stage. Furthermore, survival analysis showed that high transcript levels of PBX4 were associated with overall survival in colon cancer patients, while low levels of PBX2 predicted improved disease-free survival in rectal cancer patients. In addition, in colon and rectal cancers, PBX proteins were notably associated with infiltration of multiple immune cells, including CD4+ T cells, CD8+ T cells, macrophages, neutrophils, B cells, and dendritic cells.Conclusion: These findings implies that PBX1 and PBX3 are potential targets for precision therapy of colorectal cancer patients and that PBX2 and PBX4 may be new prognostic markers for colorectal cancer patients.

scholarly journals Prognostic value of a metastasis-related gene signature in hepatocellular carcinoma

2020 ◽  
Author(s):  
Zhou Zhou ◽  
Yinan Jiang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Rate ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Risk Groups ◽  
Postoperative Recurrence ◽  
Gene Set Enrichment Analysis ◽  
High Recurrence Rate ◽  
Gene Set

Abstract Background: Surgery is a potential curative treatment for hepatocellular carcinoma (HCC), but postoperative recurrence occurs in majority of patients. Currently, there are no robust biomarkers to predict the disease progression or recurrence. Methods: Weighted gene correlation network analysis (WGCNA) was used to construct co-expression network. The least absolute shrinkage and selection operator (LASSO) method was applied to develop prognostic model. Survival analysis, gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were performed to assess the performance. Results: By using GSE14520 dataset, 16 hub genes associated with HCC metastasis were screened. A signature of 5 metastasis-related genes was subsequently constructed by incorporating TCGA LIHC dataset. HCC patients with high risk score have low survival rate, low disease free survival rate and high recurrence rate. The prognostic value of this 5-mRNA signature was further verified in pan-cancer datasets. A nomogram was built with excellent performance and potential clinical application for prognosis. GSVA and GSVA revealed that metabolic pathways are distinct between high- and low-risk groups. Conclusions: We have established a 5-mRNA signature and a nomogram that can efficiently predict metastasis, recurrence and patient survival in HCC.

GINS1/2/3/4 Upregulation Predicts Poor Prognosis in Human Sarcoma

2021 ◽  
Author(s):  
Gen Wu ◽  
Ziyuan Chen ◽  
Tong Wu ◽  
Jian Zhou ◽  
Qunyan Tian ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Family Members ◽  
Disease Free Survival ◽  
Cancer Cell Line ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Human Sarcoma ◽  
Kaplan Meier Plotter

Abstract Background: GINS family was reported to be highly expressed in many tumors. However, the association of GINS family with human sarcoma remained unknown. This study was undertaken to explore the expression and prognostic value of GINS family in human sarcoma.Methods: In terms of the expression levels of mRNA for GINS family members, a particular contrast in various cancers, especially human sarcoma, was conducted through ONCOMINE and GEPIA and CCLE databases. Kaplan-Meier Plotter was used to identify the prognostic value of GINS family in sarcoma.Results: We discovered that the mRNA expression levels of GINS1, GINS2, GINS3, and GINS4 were all higher in the majority of tumor tissues than in normal samples, of course, including sarcoma. Through the Cancer Cell Line Encyclopedia (CCLE), all the four members (GINS1, GINS2, GINS3, GINS4) expression were observed in high levels in sarcoma cell lines. In Gene Expression Profiling Analysis (GEPIA) and Kaplan-Meier Plotter, our results indicated that the poor overall survival (OS), disease-free survival (DFS) and relapse free survival (RFS) were tightly associated with the increased expression of GINS genes. Conclusion: The four GINS family members are all the prognostic biomarkers for the prognosis of human sarcoma.

scholarly journals Exploring the Prognostic Value and Biological Function of CPNE1 Gene in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Jinfang Su ◽  
Yongbiao Huang ◽  
Yali Wang ◽  
Rui Li ◽  
Wanjun Deng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Liver Cancer ◽  
Western Blot ◽  
Prognostic Value ◽  
Enrichment Analysis ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Target Enrichment ◽  
Hcc Cells

Abstract BackgroundLiver hepatocellular carcinoma (LIHC), the major histology subtype of primary liver cancer, accounts for 70-80% proportion of total liver cancer cases. Copine1 (CPNE1), the first discovered CPNE1 family member, participates in the process of carcinogenesis and development of diverse tumors. Our study aimed to investigate the expression and prognostic value of CPNE1 gene in hepatocellular carcinoma (HCC), to explore its functional network in HCC and its effects on biological behaviors such as proliferation, migration and invasion of HCC cells, and to explore its related signaling pathways.METHODSHCCDB, CCLE and HPA online databases were used to explore the expression of CPNE1 gene in HCC tissues; LinkedOmics online database was used to analyze the co-expression network of CPNE1 in hepatocellular carcinoma, and gene set enrichment analysis (GSEA) was used for GO functional annotation, KEGG pathway enrichment analysis, kinase target enrichment, miRNA target enrichment and transcription factor target enrichment analysis. The expression levels of CPNE1 in normal hepatocytes and several hepatocellular carcinoma cell lines were detected by RT-qPCR, and finally HepG2 and MHCC-97H cells were selected to construct CPNE1 knockdown cell lines by transfection with siRNA, and the knockdown efficiency was detected by Western Blot and RT-qPCR. The effect of CPNE1 knockdown on the proliferation of hepatocellular carcinoma cells was examined by CCK8 assay and clone formation assay; the effect of CPNE1 knockdown on the migration ability of hepatocellular carcinoma cells was assessed by cell scratch assay and Transwell cell migration assay; finally, the expression of related signaling pathway proteins was examined by Western Blot. The correlation of CPNE1 expression with immune infiltration and immune checkpoint molecules in HCC tissues was analyzed using TIMER online database.RESULTSAnalysis in several databases showed that CPNE1 was highly expressed in HCC tissues and significantly correlated with sex, age, cancer stage and tumor grade. Overall survival (OS) was significantly lower in patients with high CPNE1 expression than in patients with low CPNE1 expression, and CPNE1 could be used as an independent prognostic indicator for HCC. GSEA analysis showed that co-expressed genes of CPNE1 were mainly involved in biological processes such as establishment of protein localization to membrane, ribonucleoprotein complex biogenesis and lipid localization. Q-PCR showed that CPNE1 expression was upregulated in HCC cells compared with normal hepatocytes, and knockdown of CPNE1 gene inhibited the AKT/P53 pathway, resulting in decreased proliferation, migration and invasion of HCC cells. The level of CPNE1 expression in HCC was significantly and positively correlated with the level of infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p<0.001), and with the expression of immune checkpoint molecules PDCD1, CD274, CTLA4, LAG3, HAVCR2, and TIGIT.CONCLUSIONThe expression of CPNE1 was significantly higher in HCC tissues than in normal liver tissues, and high CPNE1 expression was associated with poor prognosis. Knockdown of CPNE1 inhibited AKT/P53 pathway activation and suppressed HCC cell proliferation and migration. There was a significant correlation between CPNE1 expression and tumor immune infiltration in HCC.

scholarly journals The Prognostic value of the Fibrinogen to pre-albumin ratio in malignant tumors of the digestive system: a systematic review and meta-analysis

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Baibei Li ◽  
Huachu Deng ◽  
Ziyan Zhou ◽  
Bo Tang
Keyword(s):  
Systematic Review ◽  
Prognostic Value ◽  
Digestive System ◽  
Malignant Tumors ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Poor Overall Survival ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Albumin Ratio

Abstract Background In recent years, the Fibrinogen to pre-albumin ratio (FPR) has been reported in many studies to be significantly associated with the prognosis of various cancers. This systematic review and meta-analysis aimed to investigate the prognostic value of FPR in malignant tumors of the digestive system based on available evidence. Methods The relevant articles published before July 1, 2021, were systematically retrieved from electronic databases to evaluate the effect of Fibrinogen to pre-albumin ratio (FPR) on the prognosis of patients with malignant digestive system tumors and calculate the hazard ratio (HR) and the corresponding 95% confidence interval (CI). Result Thirteen articles, all from China, including 15 cohort studies and a total of 5116 cases, were included in this study. A high FPR was associated with poor overall survival (HR = 1.88, 95%CI 1.53–2.32, P < 0.001), recurrence-free survival (HR = 2.29, 95%CI 1.91–2.76, P < 0.001), progression-free survival (HR = 1.96, 95%CI: 1.33–2.90, P = 0.001), complications (HR = 1.78, 95%CI: 1.06–3.00, P = 0.029), disease-free survival (HR = 1.46, 95%CI: 1.08–1.97, P = 0.013) was significantly associated with cancer-specific survival (HR = 1.44, 95%CI: 1.15–1.79, P = 0.001). Even though intergroup differences were present, FPR was strongly associated with overall and relapse-free survival, and sensitivity analysis suggested that our results were stable. Conclusion FPR can be used as a valuable indicator to predict the prognosis of patients with malignant digestive system tumors.

scholarly journals Double-targeting CDCA8 and E2F1 inhibits the growth and migration of malignant glioma

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xiaoxiong Wang ◽  
Heping Wang ◽  
Jiajun Xu ◽  
Xu Hou ◽  
Haoqiang Zhan ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Malignant Tumors ◽  
Disease Free Survival ◽  
High Grade Glioma ◽  
Poor Overall Survival ◽  
Survival Prognosis ◽  
Who Grade ◽  
And Migration

AbstractHigh-grade glioma is the most common and aggressive primary brain tumor in adults with poor therapeutic efficiency and survival prognosis. Cell division cycle associated 8 (CDCA8) has been well known as a cell cycle regulator and tumor promotor in various malignant tumors. However, its biological role in glioma still remains unclear. Our results showed that high level of CDCA8 was significantly correlated with advanced WHO grade and poor overall survival and disease-free survival prognosis. In vitro and in vivo investigations demonstrated that CDCA8 promoted the glioma malignancy by promoting cell proliferation, cell migration, and inhibiting cell apoptosis. Moreover, we found its synergetic biological protein—E2F1 by the gene microarray chip. In this study, we revealed that CDCA8 synergized with E2F1 facilitated the proliferation and migration of glioma. In conclusion, our study provides a novel promising therapeutic targets and prognostic biomarkers for malignant glioma treatment.

scholarly journals In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382098682
Author(s):  
Zhipeng Zhu ◽  
Jiuhua Xu ◽  
Xiaofang Wu ◽  
Sihao Lin ◽  
Lulu Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Subgroup Analysis ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
The Impact

Background: ADAMTS5 has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of ADAMTS5 in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC. Methods: Firstly, the association of ADAMTS5 expression and clinicopathological parameters was evaluated by in GSE14520. Next, ADAMTS5 expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value of ADAMTS5 in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms. Result: The expression of ADAMTS5 was positively correlated with the development of HCC. Next, high ADAMTS5 expression was significantly associated with poorer survival (all P < 0.05) and the impact of ADAMTS5 on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that ADAMTS5 overexpression was significantly associated with poorer OS in patients with HCC. Finally, ADAMTS5 might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC. Conclusion: ADAMTS5 may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.

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.

scholarly journals LncRNA SNHG17 Contributes to Proliferation, Migration, and Poor Prognosis of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yue Luo ◽  
Junhao Lin ◽  
Jiakang Zhang ◽  
Zhenghui Song ◽  
Dayong Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Rna Sequencing ◽  
Expression Pattern ◽  
Cell Lines ◽  
Disease Free Survival ◽  
Loss Of Function ◽  
Poor Overall Survival ◽  
Apoptotic Pathway ◽  
Qrt Pcr

Long noncoding RNAs (lncRNAs) have been substantially reported to have critical roles in regulating tumorigenesis in recent years. However, the expression pattern and biological function of SNHG17 in hepatocellular carcinoma (HCC) remain unclear. Bioinformatics analysis and qRT-PCR were performed to detect the expression pattern of SNHG17 in HCC tissues, adjacent nontumorous tissues, and cell lines. The effect of SNHG17 on proliferation, migration, and apoptosis of HCC was investigated by knockdown and overexpressing SNHG17 in HCC cell lines. RNA sequencing was utilized to explore the underlying mechanism. Utilizing publicly available TCGA-LIHC, GSE102079 HCC datasets, and qRT-PCR, we found SNHG17 was significantly upregulated in HCC tissues and cell lines and was notably associated with larger tumor size, poorly differentiation, presence of vascular invasion, and advanced TNM stage. Furthermore, gain- and loss-of-function studies demonstrated that SNHG17 promoted cell proliferation and migration and inhibited apoptosis of HCC. By employing RNA sequencing, we found knockdown of SNHG17 caused 1037 differentially expressed genes, highly enriched in several pathways, including metabolic, PI3K-Akt, cell adhesion, regulation of cell proliferation, and apoptotic pathway; among them, 92 were overlapped with SNHG17-related genes in the TCGA-LIHC dataset. Furthermore, ERH, TBCA, TDO2, and PDK4 were successfully validated and found significantly dysregulated in HCC tissues. Moreover, HCC patients with higher SNHG17 expression had a relatively poor overall survival and disease-free survival, and ERH and PDK4 also played a marked role in the prognosis of HCC. Broadly, our findings illustrate that SNHG17 acts as a noncoding oncogene in HCC progression, suggesting its potential value as a novel target for HCC therapy.

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