scholarly journals High Expression of PDZ-binding Kinase Is Correlated With Poor Prognosis and Immune Infiltrates in Hepatocellular Cacinoma

2021 ◽  
Author(s):  
Wei Mu ◽  
Yaoli Xie ◽  
Jinhu Li ◽  
Runzhi Yan ◽  
Jingxian Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Protein Kinase ◽  
Receiver Operating Characteristic ◽  
Roc Curve ◽  
Poor Prognosis ◽  
Operating Characteristic ◽  
High Expression

Abstract BackgroundPDZ-binding kinase (PBK) encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. There is evidence that overexpression of this gene is associated with tumorigenesis. However, the role of PBK in hepatocellular carcinoma (HCC) remain unclear. Therefore, we evaluated the prognostic role of PBK and its correlation with immune infiltrates in Hepatocellular Carcinoma.MethodsThe expression of PBK in pan-cancers was studied by Onconmine and TIMER. The expression of PBK in HCC patients and its relationship with clinicopathological characteristics were analyzed using The Gene Expression Profiling Interactive Analysis (GEPIA), The human protein atlas database (HPA), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic value of PBK in HCC patients. The relationship between PBK and prognosis of HCC was performed by GEPIA and Kaplan Meier plotter web tool. The correlations between the clinical characteristics and overall survival were analyzed by Univariate Cox regression and Multivariate Cox hazards regression to identify possible prognostic factors for HCC patients. LinkedOmics was applied to investigate co-expression associated with PBK and to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The network map of PBK and related genes is constructed by GeneMANIA. Finally, TIMER and TISIDB were used to analyze the correlations between PBK and tumor-infiltrating immune cells.ResultsPBK was highly expressed in many types of tumors, including hepatocellular carcinoma, and was significantly related to tumor stage (P=0.0089), age (P=0.0131) and race (P=0.0024) of HCC patients. The receiver operating characteristic (ROC) curve analysis from 4 GEO databases showed that PBK is a predictive marker for HCC. Moreover, high expression of PBK correlated with poor prognosis. Multivariate Cox hazards regression showed that high expression of PBK may be an independent risk factor for overall survival in HCC patients (HR = 1.566, 95% CI=1.062-2.311, P= 0.024). The Protein–protein interaction network showed that PBK significantly interacted with LRRC47, ARAF, LGALS9B, TTK, MELK and other essential genes. Furthermore, enrichment analysis showed that PBK and co-expressed genes participated in many biological processes, cell composition, molecular functions and pathways in HCC. Finally, the immune infiltration analysis by TIMER and TISIDB indicated that PBK expression tightly correlated with the infiltration of tumor-infiltrating lymphocytes (TILs), chemokines, and receptors.ConclusionsHigh expression of PBK is significantly correlated with poor survival and immune infiltrates in hepatocellular carcinoma. Our study suggests that PBK can be used as a biomarker of poor prognosis and potential immune therapy target in hepatocellular carcinoma.

scholarly journals Pan-cancer genomic amplifications underlie a Wnt hyperactivation phenotype associated with stem cell-like features leading to poor prognosis

2019 ◽  
Author(s):  
Wai Hoong Chang ◽  
Alvina G. Lai
Keyword(s):  
Stem Cells ◽  
Overall Survival ◽  
Cancer Stem Cells ◽  
Receiver Operating Characteristic ◽  
Poor Prognosis ◽  
Operating Characteristic ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Pan Cancer ◽  
Receiver Operating

AbstractCancer stem cells pose significant obstacles to curative treatment contributing to tumor relapse and poor prognosis. They share many signaling pathways with normal stem cells that control cell proliferation, self-renewal and cell fate determination. One of these pathways known as Wnt is frequently implicated in carcinogenesis where Wnt hyperactivation is seen in cancer stem cells. Yet, the role of conserved genomic alterations in Wnt genes driving tumor progression across multiple cancer types remains to be elucidated. In an integrated pan-cancer study involving 21 cancers and 18,484 patients, we identified a core Wnt signature of 16 genes that showed high frequency of somatic amplifications linked to increased transcript expression. The signature successfully predicted overall survival rates in six cancer cohorts (n=3,050): bladder (P=0.011), colon (P=0.013), head and neck (P=0.026), pan-kidney (P<0.0001), clear cell renal cell (P<0.0001) and stomach (P=0.032). Receiver operating characteristic analyses revealed that the performance of the 16-Wnt-gene signature was superior to tumor staging benchmarks in all six cohorts and multivariate Cox regression analyses confirmed that the signature was an independent predictor of overall survival. In bladder and renal cancer, high risk patients as predicted by the Wnt signature had more hypoxic tumors and a combined model uniting tumor hypoxia and Wnt hyperactivation resulted in further increased death risks. Patients with hyperactive Wnt signaling had molecular features associated with stemness and epithelial-to-mesenchymal transition. Our study confirmed that genomic amplification underpinning pan-cancer Wnt hyperactivation and transcriptional changes associated with molecular footprints of cancer stem cells lead to increased death risks.List of AbbreviationsTCGAThe Cancer Genome AtlasKEGGKyoto Encyclopedia of Genes and GenomesGOGene OntologyROCReceiver operating characteristicAUCArea under the curveHRHazard ratioTNMTumor, node and metastasisHIFHypoxia inducible factorTFTranscription factorEMTEpithelial-to-mesenchymal transition

High expression of PPM1G is associated with the progression and poor prognosis of hepatocellular carcinoma

2021 ◽  
pp. 1-10
Author(s):  
Dan-Lei Xiong ◽  
Qian Li ◽  
Heng Wang ◽  
Wei-Li Jin ◽  
Xiao-Ming Fan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Regression ◽  
Poor Prognosis ◽  
Wnt Pathway ◽  
Signal Pathway ◽  
High Expression ◽  
Cancer Development ◽  
Pathological Grade ◽  
Essential Function

BACKGROUND: PPM1G, a member of the serine/threonine protease family, dephosphorylates various proteins and may be involved in cancer development. The role and mechanism of PPM1G in HCC still needs to be verified. OBJECTIVE: This study aims to explore the role of PPM1G in the occurrence, development and prognosis of HCC. METHODS: Using bioinformatics (UALCAN, cBioPortal, Linkedomics, STRING and GSEA) to analyze the expression of PPM1G mRNA in HCC, its clinical relevance and possible involved signaling pathways. The expression of PPM1G protein was determined by immunohistochemistry in 311 cases of HCC to evaluate the association between PPM1G and clinical features and prognosis. RESULTS: The expression of PPM1G was significantly upregulated in HCC (P< 0.001), correlated with the metastasis (P= 0.020), pathological grade of HCC (P= 0.032), microvascular invasion (P= 0.040), and HBV infection (P= 0.041). Cox multivariate regression showed high expression of PPM1G was an independent prognostic factor for HCC. Its role in HCC may relate to methylation and frequency mutation. Furthermore, the database showed PPM1G is involved in the signal pathway such as cell cycle, WNT pathway, and mTOR pathway in HCC. CONCLUSION: PPM1G showed an essential function involving in tumor-related pathways in HCC, providing a biological basis for targeted treatment of HCC clinically.

scholarly journals High SGO2 Expression Predicts Poor Overall Survival: A Potential Therapeutic Target for Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 876
Author(s):  
Min Deng ◽  
Shaohua Li ◽  
Jie Mei ◽  
Wenping Lin ◽  
Jingwen Zou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Therapeutic Target ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Clinicopathological Parameters ◽  
Potential Therapeutic Target ◽  
Poor Overall Survival

Shugoshin2 (SGO2) may participate in the occurrence and development of tumors by regulating abnormal cell cycle division, but its prognostic value in hepatocellular carcinoma (HCC) remains unclear. In this study, we accessed The Cancer Genome Atlas (TCGA) database to get the clinical data and gene expression profile of HCC. The expression of SGO2 in HCC tissues and nontumor tissues and the relationship between SGO2 expression, survival, and clinicopathological parameters were analyzed. The SGO2 expression level was significantly higher in HCC tissues than in nontumor tissues (p < 0.001). An analysis from the Oncomine and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases also demonstrated that SGO2 was upregulated in HCC (all p < 0.001). A logistic regression analysis revealed that the high expression of SGO2 was significantly correlated with gender, tumor grade, pathological stage, T classification, and Eastern Cancer Oncology Group (ECOG) score (all p < 0.05). The overall survival (OS) of HCC patients with higher SGO2 expression was significantly poor (p < 0.001). A multivariate analysis showed that age and high expression of SGO2 were independent predictors of poor overall survival (all p < 0.05). Twelve signaling pathways were significantly enriched in samples with the high-SGO2 expression phenotype. Ten proteins and 34 genes were significantly correlated with SGO2. In conclusion, the expression of SGO2 is closely related to the survival of HCC. It may be used as a potential therapeutic target and prognostic marker of HCC.

scholarly journals High Expression of SRD5A3 in Human Hepatocellular Carcinoma (HCC) Predicts Poor Prognosis: A Study Based on TCGA Data

2021 ◽  
Author(s):  
Jing Xue ◽  
Xianzhao Yang ◽  
Feng Jiang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Cox Regression ◽  
High Expression ◽  
Th2 Cells ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Pathologic Features

Abstract Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Steroid 5 alpha-reductase 3 (SRD5A3) was reported to be up-regulated in many types of cancer. However, its expression and role in HCC remains to be elucidated. We aim to evaluate the significance of SRD5A3 expression in HCC by using analysis of a public dataset from The Cancer Genome Atlas (TCGA).Methods: The relationship between clinical pathologic features and SRD5A3 were analyzed with the Kolmogorov‐Smirnov test and the logistic regression. Cox regression and the Kaplan-Meier method were used to assess the clinicopathologic characteristics associated with overall survival (OS) in TCGA patients. In addition, GSEA was used to predict potential hallmarks associated with different expression of SRD5A3 on transcriptional sequences from TCGA database.Results: SRD5A3 was highly expressed in HCC tumor tissue compared to normal tissue. A total of 184 upregulated DEGs (differentially expressed genes) and 58 downregulated DEGs were identified between high expression and low expression of SRD5A3. Among them, 22 hub genes mainly belonging to the keratin and MUC family demonstrated by connectivity degree in the PPI network were screened out. Kaplan-Meier method showed that HCC patients in the high SRD5A3 expression group had poorer overall survival (OS, HR=2.26(1.58-3.24), p<0.001). In addition, cell cycle mitotic, cell cycle checkpoints, mitotic nuclear division, Q-glycan processing, protein O-linked glycosylation were differentially enriched in the high SRD5A3 expression phenotype pathway. In addition, SRD5A3 expression level has significant correlations with infiltrating levels of Th17 (R = -0.238, p < 0.001), Cytotoxic cells (R = -0.234, p < 0.001) and Th2 cells (R = 0.258, p < 0.001) in HCC.Conclusions: High expression of SRD5A3 was significantly correlated with poor prognosis in HCC patients. It may be a potential biomarker in HCC.

Proline-Directed Protein Kinase FA Is a Powerful and Independent Prognostic Predictor for Progression and Patient Survival of Hepatocellular Carcinoma

2006 ◽  
Vol 24 (23) ◽  
pp. 3780-3788 ◽  
Author(s):  
Yu-Chen Hsu ◽  
Hsiao-Hui Fu ◽  
Yung-Ming Jeng ◽  
Po-Huang Lee ◽  
Shiaw-Der Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Protein Kinase ◽  
Patient Survival ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Prognostic Role ◽  
Free Survival ◽  
Disease Free

Purpose Molecular, cellular, and animal studies have established that overexpressed proline-directed protein kinase FA (PDPK FA) is essential for the development of tumorigenesis, invasion, and metastasis of human cancer cells. However, the prognostic role of PDPK FA in cancer patients remains largely unknown. In this study, association of PDPK FA expression with poor prognosis of hepatocellular carcinoma (HCC) patients was examined. Patients and Methods PDPK FA expression in the resected tumors of 134 HCC patients (112 men and 22 women) with ages ranging from 33 to 83 years (mean, 55 years) was analyzed by immunohistochemistry. Highly condensed cytoplasmic and nuclear PDPK FA associated with tumor cells was used as the major scoring parameter for positive PDPK FA expression. Results Approximately 68% of the patients (91 of 134) exhibited positive PDPK FA expression. Patients with positive PDPK FA showed poorer disease-free survival and overall survival (P < .001). Cox multivariate regression analysis further established PDPK FA as the strongest independent prognosticator for progression and patient survival of HCC (hazard ratio [HR], 2.878; 95% CI, 1.634 to 5.067 for disease-free survival; and HR, 5.035; 95% CI, 2.137 to 11.866 for overall survival; P < .001). Conclusion Consistent with PDPK FA’s essential role in the development of highly malignant phenotypes, the present study establishes the potential prognostic role of PDPK FA in progression and patient survival of surgically resected primary HCC. Taken together, PDPK FA represents a new modifiable signal-transducing target for prognostic prediction and adjuvant treatment of patients with aggressive HCC after hepatic resection.

scholarly journals High HSPA8 expression predicts adverse outcomes of acute myeloid leukemia

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Li ◽  
Zheng Ge
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Cell Function ◽  
Adverse Outcomes ◽  
High Expression ◽  
Micro Rnas ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) remains one of the most common hematological malignancies, posing a serious challenge to human health. HSPA8 is a chaperone protein that facilitates proper protein folding. It contributes to various activities of cell function and also is associated with various types of cancers. To date, the role of HSPA8 in AML is still undetermined. Methods In this study, public datasets available from the TCGA (Cancer Genome Atlas) and GEO (Gene Expression Omnibus) were mined to discover the association between the expression of HSPA8 and clinical phenotypes of CN-AML. A series of bioinformatics analysis methods, including functional annotation and miRNA-mRNA regulation network analysis, were employed to investigate the role of HSPA8 in CN-AML. Results HSPA8 was highly expressed in the AML patients compared to the healthy controls. The high HSPA8 expression had lower overall survival (OS) rate than those with low HSPA8 expression. High expression of HSPA8 was also an independent prognostic factor for overall survival (OS) of CN-AML patients by multivariate analysis. The differential expressed genes (DEGs) associated with HSPA8 high expression were identified, and they were enriched PI3k-Akt signaling, cAMP signaling, calcium signaling pathway. HSPA8 high expression was also positively associated with micro-RNAs (hsa-mir-1269a, hsa-mir-508-3p, hsa-mir-203a), the micro-RNAs targeted genes (VSTM4, RHOB, HOBX7) and key known oncogenes (KLF5, RAN, and IDH1), and negatively associated with tumor suppressors (KLF12, PRKG1, TRPS1, NOTCH1, RORA). Conclusions Our research revealed HSPA8 as a novel potential prognostic factor to predict the survival of CN-AML patients. Our data also revealed the possible carcinogenic mechanism and the complicated microRNA-mRNA network associated with the HSPA8 high expression in AML.

Bioinformatics Analysis of The Expression of ATP Binding Cassette Transporters and The Screening of Regulatory Genes in PTEN/PI3K/Akt/mTOR Signaling Pathway in The Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Tingdan Zheng ◽  
Wuqi Song ◽  
Aiying Yang
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Bioinformatics Analysis ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Short Term ◽  
Term Survival ◽  
Log Rank Test ◽  
Short Term Survival

Abstract Objective Here we performed the Bioinformatics analysis on the data from The Cancer Genome Atlas (TCGA), in order to find the correlation between the expression of ATP Binding Cassette (ABC) Transporters’ genes and hepatocellular carcinoma (HCC) prognosis; Methods Transcriptome profiles and clinical data of HCC were obtained from TCGA database. Package edgeR was used to analyze differential gene expression. Patients were divided into low-ABC expression and high-ABC expression groups based on the median expression level of ABC genes in cancer. The overall survival and short-term survival (n= 341) of the two groups was analyzed using the log-rank test and Wilcoxon test; Results We found that ABC gene expression was correlated with the expression of PIK3C2B (p<0.001, ABCC1: r=0.27; ABCC10: r=0.57; ABCC4: r=0.20; ABCC5: r=0.28; ABCB9: r=0.17; ABCD1: r=0.21). All patients with low-ABC expression showed significantly increased overall survival. Significantly decreased overall survival (Log-rank test: p<0.05, Wilcoxon test: p<0.05) was found in patients with high expression of ABCC1 (HR=1.58), ABCD1 (HR=1.45), ABCC4 (HR=1.56), and ABCC5 (HR=1.64), while decreased short-term survival (Log-rank test: p>0.05, Wilcoxon test: p<0.05) was correlated with the increased expression of ABCC10 (HR=1.29), PIK3C2B (HR=1.29) and ABCB9 (HR=1.23); Conclusions Our findings indicate that the specific ABC gene expression correlates with the prognosis of HCC. Therefore, ABC expression profile could be a potential indicator for HCC patients.

GCSF As a Potential Molecular Target for Overall Survival of Hepatocellular Carcinoma

2021 ◽  
Vol 24 ◽  
Author(s):  
Heng Cao ◽  
Peng Guo ◽  
Xiaohui Wu ◽  
Jiankun Li ◽  
Chenlong Ge ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Survival Analysis ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Basic Research ◽  
Clinical Samples ◽  
Tumor Diameter ◽  
Overall Survival Analysis

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of digestive tract in the world. Therefore, it is important to carry out studies on the molecular mechanisms of early diagnosis and treatment of HCC to reduce mortality. Methods: Bioinformatic analysis was performed to explore the significant role of GCSF on the occurrence and development of neoplasm. Differently expressed genes (DEGs) were screened, and the significant hub genes related with GCSF were identified by the multiple algorithms of Cytoscape. Functional annotation for DEGs, pathological stage and overall survival analysis were implemented. In addition, the verification for the role of GCSF on HCC was made via the clinical samples. A total of 70 participates diagnosed as HCC were recruited from November 2014 to November 2019. The immunohistochemistry assay, qRT-PCR, receiver operating characteristic (ROC) curves, and overall survival analysis were carried out. Results: GCSF was related with the tumor size, and the expression of GCSF was up-regulated in hepatocellular carcinoma tissues. The enrichment results of GO and KEGG analysis were mainly enriched in “Inflammatory response”, “Protein binding”, “Metabolic pathways”, and “Proteasome”. The tumor diameter (P < 0.001), and survival time (P < 0.001) were significantly associated with expression of GCSF via the verification of clinical data. The univariate and multivariate Cox proportional regression analysis manifested that high expression of GCSF in patients with HCC was related to poor OS. Conclusion: The expression level of GCSF is significantly associated with the prognostic survival of HCC, and it is expected to become a new prognostic marker of HCC, providing a novel idea for future basic research as well as targeted therapy.

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