scholarly journals CELSR3 mRNA expression is increased in hepatocellular carcinoma and indicates poor prognosis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7816 ◽  
Author(s):  
Xuefeng Gu ◽  
Hongbo Li ◽  
Ling Sha ◽  
Yuan Mao ◽  
Chuanbing Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Cell Line ◽  
Roc Curve ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Dna Recombination ◽  
Gene Set Enrichment Analysis ◽  
Kaplan Meier

Objective Hepatocellular carcinoma (HCC) is a disease that is associated with high mortality; currently, there is no curative and reliable treatment. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) is the key signaling molecule in the wingless and INT-1/planar cell polarity (WNT/PCP) pathway. This study aimed to elucidate the prognostic significance of CELSR3 in HCC patients. Methods The Cancer Genome Atlas (TCGA) database, the Cancer Cell Line Encyclopedia (CCLE) database and the Gene Expression Omnibus (GEO) database were used to analyze the expression of CELSR3 mRNA in HCC samples and cells. The relationship between CELSR3 mRNA and clinical features was assessed by the chi-square test. the diagnostic and predictive value of CELSR3 mRNA expression were analyzed using the receiver operating characteristic (ROC) curve. Kaplan–Meier curve and Cox regression analyses were performed to assess the prognostic value of CELSR3 mRNA in HCC patients. Finally, all three cohorts database was used for gene set enrichment analysis(GSEA) and the identification of CELSR3-related signal transduction pathways. Results The expression of CELSR3 mRNA was upregulated in HCC, and its expression was correlated with age (P = 0.025), tumor status (P = 0.022), clinical stage (P = 0.003), T classification (P = 0.010), vital status (P = 0.001), and relapse (P = 0.005). The ROC curve assessment indicated that CELSR3 mRNA expression has high diagnostic value in HCC and in the subgroup analysis of stage. In addition, the Kaplan-Meier curve and Cox analyses suggested that patients with high CELSR3 mRNA expression have a poor prognosis, indicating that CELSR3 mRNA is an independent prognostic factor for the overall survival of HCC patients. GSEA showed that GO somatic diversification of immune receptors, GO endonuclease activity, GO DNA repair complex and GO somatic cell DNA recombination, were differentially enriched in the meta-GEO cohort, the HCC cell line cohort and the TCGA cohort of the high CELSR3 mRNA expression phenotype. Conclusion Our results indicate that CELSR3 mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients.

scholarly journals Eg5 Overexpression Is Predictive of Poor Prognosis in Hepatocellular Carcinoma Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Can Liu ◽  
Nan Zhou ◽  
Jieying Li ◽  
Jun Kong ◽  
Xi Guan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Protein Expression ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tnm Stage ◽  
Tissue Samples ◽  
Cycle Arrest ◽  
Kaplan Meier

Eg5 (kinesin spindle protein) plays an essential role in mitosis. Inhibition of Eg5 function results in cell cycle arrest at mitosis, which leads to cell death. To date, Eg5 expression and its prognostic significance have not been studied in hepatocellular carcinoma (HCC). In this study, 26 freshly frozen HCC tissue samples and matched peritumoral tissue samples were evaluated with a one-step qPCR test and immunohistochemical (IHC) analysis was conducted on 156 HCC samples to investigate the relationships among Eg5 expression, clinicopathological factors, and prognosis. Eg5 mRNA and protein expression levels were significantly higher in HCC tissues relative to matched noncancerous tissues (p<0.05). High Eg5 protein expression was significantly related to liver cirrhosis (p=0.038) and TNM stage (p=0.008). Kaplan-Meier survival and Cox regression analyses revealed that Eg5 overexpression (p=0.001), liver cirrhosis (p=0.009), and TNM stage (p=0.025) were independent prognostic factors for overall survival. These findings indicate that Eg5 expression can be used as a biomarker of poor prognosis and as a novel therapeutic target for HCC.

Prognostic value of biglycan in gastric cancer

2020 ◽  
Author(s):  
Sizhe Hu ◽  
Peipei Li ◽  
Chenying Wang ◽  
Xiyong Liu
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Mrna Levels ◽  
Gene Signatures ◽  
Kaplan Meier

Abstract Background: BGN (biglycan) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer.Material and Methods: Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets( n= 64, n=432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Bioinformatic analysis predicted the putative transcription factors of BGN.Results: For gastric cancer, the mRNA expression level of BGN in tumor tissues was significantly higher than that in normal tissues. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN significantly enriched metastasis and poor prognosis gene signatures, revealing that BGN might be associated with cell proliferation, poor differentiation, high invasiveness of gastric cancer. Meanwhile, the putative transcription factors, including AR, E2F1, and TCF4, weres predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.

scholarly journals High Expression of PXN Predicts a Poor Prognosis in Acute myeloid leukemia

2021 ◽  
Author(s):  
xinwen zhang ◽  
Hao Xiong ◽  
Jialin Duan ◽  
Xiaomin Chen ◽  
Yang Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Receive Treatment ◽  
To Receive ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is one of the common malignant diseases of hematopoietic system. Paxillin ( PXN ) is an important part of focal adhesions (FAs), which is related to the poor prognosis of many kinds of malignant tumors. However, no research has focused on the expression of PXN in AML. We aimed to investigate the expression of PXN in AML and its prognostic significance. Methods: Using GEPIA and UALCAN database to analyze the expression of PXN in AML patients and its prognostic significance. Bone marrow samples of newly diagnosed AML patients were collected to extract RNA, and qRT-PCR was used to detect the expression of PXN . The prognosis was followed up. Chi-square test was used to analyze the relationship between PXN expression and clinical laboratory characteristics. Kaplan-Meier analysis was used to draw survival curve, and Cox regression analysis was used to analyze the independent factors affecting the prognosis of patients with AML. The co-expression genes of PXN were analyzed by LinkedOmics to explore its biological significance in AML. Results: Kaplan-Meier analysis showed that the overall survival time of AML patients was related to whether to receive treatment and PXN expression(P<0.05). COX regression analysis showed that whether to receive treatment (HR=0.227，95%CI=0.075-0.689， P =0.009) and high expression of PXN (HR=4.484，95%CI=1.449-13.889， P =0.009) were independent poor prognostic factors in patients with AML. Conclusion: PXN is highly expressed in AML patient, and high PXN expression is an indicator of poor prognosis in AML patient.

scholarly journals Decreased DHRS1 expression is a novel predictor of poor survival in patients with hepatocellular carcinoma

2021 ◽  
Vol 15 (15) ◽  
pp. 1319-1331
Author(s):  
Li Li ◽  
Hui-Jing Situ ◽  
Wen-Cheng Ma ◽  
Xuan Liu ◽  
Lu-Lu Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Multiple Data ◽  
Kaplan Meier ◽  
Survival Gene ◽  
Mrna And Protein Expression

Aim: To investigate the effect of aberrant expression of DHRS1 on hepatocellular carcinoma (HCC). Materials & methods: Kaplan–Meier and Cox regression analyses were performed to evaluate the correlation between DHRS1 and overall survival. Gene set enrichment analysis was performed to explore the potential function of DHRS1 in HCC. Results: Multiple data analysis revealed that DHRS1 mRNA and protein expression level were remarkably lower in HCC than that in normal tissues. In survival analysis, patients with low DHRS1 expression presented a poorer prognosis, and was an independent risk factor for HCC. Conclusion: Decreased DHRS1 expression may be a potential predictor of poor prognosis in HCC.

scholarly journals Identification of the HMMR Gene as a Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma Based on Integrated Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Honglan Guo ◽  
Qinqiao Fan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Roc Curve ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Roc Curve Analysis ◽  
Cox Regression Analysis ◽  
Normal Tissues

Background. We aimed to investigate the expression of the hyaluronan-mediated motility receptor (HMMR) gene in hepatocellular carcinoma (HCC) and nonneoplastic tissues and to investigate the diagnostic and prognostic value of HMMR. Method. With the reuse of the publicly available The Cancer Genome Atlas (TCGA) data, 374 HCC patients and 50 nonneoplastic tissues were used to investigate the diagnostic and prognostic values of HMMR genes by receiver operating characteristic (ROC) curve analysis and survival analysis. All patients were divided into low- and high-expression groups based on the median value of HMMR expression level. Univariate and multivariate Cox regression analysis were used to identify prognostic factors. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism of the HMMR genes involved in HCC. The diagnostic and prognostic values were further validated in an external cohort from the International Cancer Genome Consortium (ICGC). Results. HMMR mRNA expression was significantly elevated in HCC tissues compared with that in normal tissues from both TCGA and the ICGC cohorts (all P values <0.001). Increased HMMR expression was significantly associated with histologic grade, pathological stage, and survival status (all P values <0.05). The area under the ROC curve for HMMR expression in HCC and normal tissues was 0.969 (95% CI: 0.948–0.983) in the TCGA cohort and 0.956 (95% CI: 0.932–0.973) in the ICGC cohort. Patients with high HMMR expression had a poor prognosis than patients with low expression group in both cohorts (all P < 0.001 ). Univariate and multivariate analysis also showed that HMMR is an independent predictor factor associated with overall survival in both cohorts (all P values <0.001). GSEA showed that genes upregulated in the high-HMMR HCC subgroup were mainly significantly enriched in the cell cycle pathway, pathways in cancer, and P53 signaling pathway. Conclusion. HMMR is expressed at high levels in HCC. HMMR overexpression may be an unfavorable prognostic factor for HCC.

scholarly journals NUCKS1 Acts As A Promising Novel Bio-Marker in The Prognosis of Patients with Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Xianfeng Zhang ◽  
Xianjun Zhang ◽  
Xinguo Li ◽  
Hongbing Bao ◽  
Guang Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Prognostic Value ◽  
Cox Regression ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Kinase Substrate ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Relative Mrna Expression

Abstract Background: Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) was over-expressed in some tumors, including hepatocellular carcinoma (HCC). However, the clinical significance of NUCKS1 in HCC was still unclear. The aim of this study was to explore the expression and prognostic value of NUCKS1 in HCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of NUCKS1 in HCC tissues and corresponding adjacent normal tissues. The relationship between NUCKS1 expression and clinical characteristics of patients was analyzed by c2 test. Kaplan-Meier method and cox regression analysis were applied to estimate the prognostic value of NUCKS1 in HCC. Results: Compared with normal tissues, the relative mRNA expression level of NUCKS1 was significantly up-regulated in HCC tissues (P < 0.001). And high NUCKS1 expression was closely associated with tumor differentiation, TNM stage, vascular invasion and metastasis (P < 0.05). Kaplan-Meier analysis revealed that the overall survival of HCC patients with low expression of NUCKS1 was obviously longer than those with high NUCKS1 expression (log rank test, P = 0.001). NUCKS1 was an independent prognostic factor of HCC patients via univariate and multivariate cox regression analyses.Conclusions: NUCKS1 may be correlated with the progression of HCC and may serve as a potential factor for the prognosis of this disease.

scholarly journals Identification and Validation of Ubiquitin-Specific Proteases as a Novel Prognostic Signature for Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenkai Ni ◽  
Saiyan Bian ◽  
Mengqi Zhu ◽  
Qianqian Song ◽  
Jianping Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Cancer Genome ◽  
Advanced Tumor Stage ◽  
Genomic Alterations ◽  
Advanced Tumor

PurposeUbiquitin-specific proteases (USPs), as a sub-family of deubiquitinating enzymes (DUBs), are responsible for the elimination of ubiquitin-triggered modification. USPs are recently correlated with various malignancies. However, the expression features and clinical significance of USPs have not been systematically investigated in hepatocellular carcinoma (HCC).MethodsGenomic alterations and expression profiles of USPs were investigated in CbioPortal and The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) dataset. Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were conducted to establish a risk signature for HCC prognosis in TCGA LIHC cohort. Subsequently, Kaplan-Meier analysis, receiver operating characteristic (ROC) curves and univariate/multivariate analyses were performed to evaluate the prognostic significance of the risk signature in TCGA LIHC and international cancer genome consortium (ICGC) cohorts. Furthermore, we explored the alterations of the signature genes during hepatocarcinogenesis and HCC progression in GSE89377. In addition, the expression feature of USP39 was further explored in HCC tissues by performing western blotting and immunohistochemistry.ResultsGenomic alterations and overexpression of USPs were observed in HCC tissues. The consensus analysis indicated that the USPs-overexpressed sub-Cluster was correlated with aggressive characteristics and poor prognosis. Cox regression with LASSO algorithm identified a risk signature formed by eight USPs for HCC prognosis. High-risk group stratified by the signature score was correlated with advanced tumor stage and poor survival HCC patients in TCGA LIHC cohort. In addition, the 8-USPs based signature could also robustly predict overall survival of HCC patients in ICGC(LIRI-JP) cohort. Furthermore, gene sets enrichment analysis (GSEA) showed that the high-risk score was associated with tumor-related pathways. According to the observation in GSE89377, USP39 expression was dynamically increased with hepatocarcinogenesis and HCC progression. The overexpression of USP39 was further determined in a local HCC cohort and correlated with poor prognosis. The co-concurrence analysis suggested that USP39 might promote HCC by regulating cell-cycle- and proliferation- related genes.ConclusionThe current study provided a USPs-based signature, highlighting its robust prognostic significance and targeted value for HCC treatment.

scholarly journals Upregulation of LIMK1 Is Correlated With Poor Prognosis and Immune Infiltrates in Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Guojun Lu ◽  
Ying Zhou ◽  
Chenxi Zhang ◽  
Yu Zhang
Keyword(s):  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Roc Curve ◽  
Poor Prognosis ◽  
Expression Profiles ◽  
Immune Therapy ◽  
Functional Enrichment ◽  
Normal Tissues ◽  
Ppi Networks ◽  
Kaplan Meier

BackgroundProtein-coding gene LIM Domain Kinase 1 (LIMK1) is upregulated in various tumors and reported to promote tumor invasion and metastasis. However, the prognostic values of LIMK1 and correlation with immune infiltrates in lung adenocarcinoma are still not understood. Therefore, we evaluated the prognostic role of LIMK1 and its correlation with immune infiltrates in lung adenocarcinoma.MethodsTranscriptional expression profiles of LIMK1 between lung adenocarcinoma tissues and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). The LIMK1 protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas. Receiver operating characteristic (ROC) curve was used to differentiate lung adenocarcinoma from adjacent normal tissues. Kaplan-Meier method was conducted to assess the effect of LIMK1 on survival. Protein-protein interaction (PPI) networks were constructed by the STRING. Functional enrichment analyses were performed using the “ClusterProfiler” package. The relationship between LIMK1 mRNA expression and immune infiltrates was determined by tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB).ResultsThe expression of LIMK1 in lung adenocarcinoma tissues was significantly upregulated than those in adjacent normal tissues. Increased LIMK1 mRNA expression was associated with lymph node metastases and high TNM stage. The ROC curve analysis showed that with a cutoff level of 4.908, the accuracy, sensitivity, and specificity for LIMK1 differentiate lung adenocarcinoma from adjacent controls were 69.5, 93.2, and 71.9%, respectively. Kaplan-Meier survival analysis showed lung adenocarcinoma patients with high- LIMK1 had a worse prognosis than those with low- LIMK1 (43.1 vs. 55.1 months, P = 0.028). Correlation analysis indicated LIMK1 mRNA expression was correlated with tumor purity and immune infiltrates.ConclusionUpregulated LIMK1 is significantly correlated with poor survival and immune infiltrates in lung adenocarcinoma. Our study suggests that LIMK1 can be used as a biomarker of poor prognosis and potential immune therapy target in lung adenocarcinoma.

scholarly journals LACTB mRNA expression is increased in pancreatic adenocarcinoma and high expression indicates a poor prognosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245908
Author(s):  
Jian Xie ◽  
Yang Peng ◽  
Xiaoyu Chen ◽  
Qigang Li ◽  
Bin Jian ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Pancreatic Adenocarcinoma ◽  
Poor Prognosis ◽  
Enrichment Analysis ◽  
Diagnostic Value ◽  
Gene Set Enrichment Analysis ◽  
Vital Status ◽  
Immune Marker ◽  
Kaplan Meier ◽  
Cancer Tissues

This study aimed to find the prognostic value of Beta-lactamase-like (LACTB) in pancreatic adenocarcinoma (PAAD) patients. The mRNA expression of LACTB was upregulated in PAAD and was correlated with vital status (P = 0.0199). The immunoreactive scores of LACTB protein in human PAAD tissues were significantly higher than those in adjacent noncancerous pancreatic tissues. Receiver operating characteristic (ROC) curve assessment showed that LACTB mRNA expression has high diagnostic value in PAAD. Kaplan-Meier curve and Cox analyses suggested that patients with high LACTB mRNA expression have a poor prognosis, indicating that LACTB mRNA is an independent prognostic factor for overall survival [hazard ratio (HR) = 1.72, P = 0.015, 95% confidence interval (CI) = 1.106–2.253] and disease-specific survival (HR = 1.97, P = 0.004, 95% CI = 1.238–3.152) of PAAD patients. Gene set enrichment analysis (GSEA) revealed that hallmark_g2m_checkpoint, hallmark_myc_targets_v1, hallmark_e2f_targets, and kegg_cell_cycle were differentially enriched in phenotypes with high LACTB expression. In addition, CDC20, CDK4, MCM6, MAD2L1, MCM2 and MCM5 were leading genes intersecting in these four pathways, and a positive correlation between mRNA expression and LACTB was observed in most normal and cancer tissues. Finally, elevated LACTB mRNA expression was significantly related to multiple immune marker sets. Our results elucidate that LACTB is involved in the development of cancer, and that high LACTB expression in patients with PAAD can predict a poor prognosis. High LACTB expression was significantly correlated with cell cycle-related genes and multiple immune marker sets.

scholarly journals Downregulation of miR-1826 Indicates a Poor Prognosis for Osteosarcoma Patients and Regulates Tumor Cell Proliferation, Migration, and Invasion

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Peng Li ◽  
Lei Wei ◽  
Wenshuai Zhu
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Migration And Invasion ◽  
Kaplan Meier ◽  
Low Levels

Background. Osteosarcoma (OS) is the most frequent bone tumor with high metastasis. This study is aimed at assessing the expression and prognostic significance of microRNA-1826 (miR-1826) in OS patients, as well as its biological function in tumor progression. Methods. Quantitative Real-Time PCR was employed to measure the expression of miR-1826 in OS tissues and cell lines. Kaplan-Meier survival analysis and Cox regression model were used to evaluate the prognostic value of miR-1826. CCK-8 and Transwell assay were conducted to investigate the effect of miR-1826 on OS cell proliferation, migration, and invasion. Results. miR-1826 expression was downregulated in OS tissues and cell lines and associated with OS patients’ clinical stage and distant metastasis. Low levels of miR-1826 were related with shorter survival time and determined as an independent prognostic indicator for the overall survival of OS patients. The overexpression of miR-1826 in OS cells led to inhibited cell proliferation, migration, and invasion. Conclusion. The decreased expression of miR-1826 predicts a poor prognosis in OS patients, and its overexpression inhibits OS cell proliferation, migration, and invasion. This newly identified miR-1826 provides a novel sight into the pathogenesis of OS and offers a candidate prognostic biomarker and therapeutic target for OS treatment.

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