scholarly journals Prognostic Significance and Gene Co-Expression Network of PLAU and PLAUR in Gliomas

2022 ◽  
Vol 11 ◽  
Author(s):  
Junhong Li ◽  
Huanhuan Fan ◽  
Xingwang Zhou ◽  
Yufan Xiang ◽  
Yanhui Liu
Keyword(s):  
Cox Regression ◽  
Prognostic Significance ◽  
High Expression ◽  
Lower Grade ◽  
Tumor Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Online Databases ◽  
Type Plasminogen Activator ◽  
Primary Glioma

The urokinase-type plasminogen activator(PLAU) and its receptor PLAUR participate in a series of cell physiological activities on the extracellular surface. Abnormal expression of PLAU and PLAUR is associated with tumorigenesis. This study aims to evaluate the prognostic value of PLAU/PLAUR transcription expression in glioma and to explore how they affect the generation and progression of glioma. In this study, online databases are applied, such as Oncomine, GEPIA, CGGA, cBioPortal, and LinkedOmics. Overexpression of PLAU/PLAUR was found to be significantly associated with clinical variables including age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. PLAU and PLAUR had a high correlation in transcriptional expression levels. High expression of PLAU and PLAUR predicted a poor prognosis in primary glioma and recurrent glioma patients, especially in lower grade gliomas. Cox regression analysis indicated that high expression of PLAU and PLAUR were independent prognostic factors for shorter overall survival in glioma patients. In gene co-expression network analysis PLAU and PLAUR and their co-expression genes were found to be involved in inflammatory activities and tumor-related signaling pathways. In conclusion, PLAU and PLAUR could be promising prognostic biomarkers and potential therapeutic targets of glioma patients.

scholarly journals Enhanced expression of miR-889 forecasts an unfavorable prognosis and facilitates cell progression in hepatocellular carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
He Wang ◽  
Huiwen Wang ◽  
Wenyu Cui ◽  
Qiao Zhang ◽  
Jing Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
High Expression ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Cox Regression Analysis

Abstract Background As a new type of molecular marker, microRNAs (miRNAs) can be used for early diagnosis and prognosis prediction of malignant tumors, and has broad clinical application prospects. This paper mainly studies the important role of miR-889 in the occurrence and development of hepatocellular carcinoma and the prognostic significance of miR-889 in hepatocellular carcinoma. Methods Quantitative real-time PCR analysis detected the expression levels of miR-889 in hepatocellular carcinoma tissues and cell lines. Kaplan-Meier curve and Cox regression analysis were used to explore the prognostic significance of miR-889 in hepatocellular carcinoma. The CCK-8 and Transwell assays assay were used to assess cell proliferation, migration, and invasion abilities ability. Results The expression of miR-889 in hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Overexpression of miR-889 was significantly associated with TNM stage, hepatitis B virus infection, and cirrhosis. Patients with high miR-889 expression had shorter overall survival than those with low miR-889 expression. And functional studies in two hepatocellular carcinoma cell lines have shown that overexpression of miR-889 significantly promoted cell proliferation, migration, and invasion in vitro. Conclusions Overall, miR-889 was upregulated in hepatocellular carcinoma tissues and cell lines, and overexpression of miR-889 promoted cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Based on our findings, high expression of miR-889 may promote the progression of hepatocellular carcinoma, and high expression of miR-889 is also forecasted for an unfavorable prognosis in hepatocellular carcinoma.

scholarly journals TMOD-01. A PROGNOSTIC NOMOGRAM MODEL AND ONLINE SOFTWARE FOR PATIENTS WITH NEWLY DIAGNOSED LOWER-GRADE GLIOMAS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i35-i35
Author(s):  
Mingzhi Han
Keyword(s):  
Cox Regression ◽  
Molecular Subtype ◽  
Age At Diagnosis ◽  
Calibration Plot ◽  
Low Grade ◽  
Lower Grade ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Survival Probabilities

Abstract The nomogram represents a statistical model that incorporates multiple risk factors to estimate individualized survival probabilities. In this study, we developed a nomogram which provides an important tool for individulized survival predicition for newly diagnosed low-grade gliomas (LGG). A total number of 582 newly diagnosed LGG patients were included; the median age was 39.93 years and 42% were female. Cox regression analysis showed that younger age at diagnosis, WHO grade II vs. III, the IDHmut-codel vs. the IDHwt, and the IDHmut-non-codel vs. the IDHwt were significantly associated with better prognosis. The adjuvant treatment following surgery showed a trend towards improved survival. Subsequently, the nomogram to estimate 60-, 90-, and 120-month survival probabilities was established. Our data showed that the age at diagnosis was the largest contributor to patient survival, followed by molecular subtype, WHO grade, treatment and gender. The calibration plot showed that the observed and the nomogram predicted OS curves were well-aligned. In addition, we also validated our nomogram for LGG patients who received postsurgical adjuvant therapy through cross-validation and the calibration plot. Finally, we developed a free online tool for this nomogram (softwarewebsite:https://rrlnnomogram.shinyapps.io/LGG_Nom_Asian/). Overall, this model should be a useful tool for counseling patients in clinical practice including treatment decisions, follow-up, and prognosis.

scholarly journals Immune-Related Gene SERPINE1 Is a Novel Biomarker for Diffuse Lower-Grade Gliomas via Large-Scale Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoming Huang ◽  
Fenglin Zhang ◽  
Dong He ◽  
Xiaoshuai Ji ◽  
Jiajia Gao ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Immune Cell ◽  
Cox Regression ◽  
Expression Patterns ◽  
Critical Role ◽  
Lower Grade ◽  
Hub Genes ◽  
Who Grade ◽  
Primary Tumors ◽  
Cox Regression Analysis

BackgroundGlioma is one of the highly fatal primary tumors in the central nervous system. As a major component of tumor microenvironment (TME), immune cell has been proved to play a critical role in the progression and prognosis of the diffuse lower-grade gliomas (LGGs). This study aims to screen the key immune-related factors of LGGs by investigating the TCGA database.MethodsThe RNA-sequencing data of 508 LGG patients were downloaded in the TCGA database. ESTIMATE algorithm was utilized to calculate the stromal, immune, and ESTIMATE scores, based on which, the differentially expressed genes (DEGs) were analyzed by using “limma” package. Cox regression analysis and the cytoHubba plugin of Cytoscape software were subsequently applied to screen the survival-related genes and hub genes, the intersection of which led to the identification of SERPINE1 that played key roles in the LGGs. The expression patterns, clinical features, and regulatory mechanisms of SERPINE1 in the LGGs were further analyzed by data mining of the TCGA database. What’s more, the above analyses of SERPINE1 were further validated in the LGG cohort from the CGGA database.ResultWe found that stromal and immune cell infiltrations were strongly related to the prognosis and malignancy of the LGGs. A total of 54 survival-related genes and 46 hub genes were screened out in the DEGs, within which SERPINE1 was identified to be significantly overexpressed in the LGG samples compared with the normal tissues. Moreover, the upregulation of SERPINE1 was more pronounced in the gliomas of WHO grade III and IDH wild type, and its expression was correlated with poor prognosis in the LGG patients. The independent prognostic value of SERPINE1 in the LGG patients was also confirmed by Cox regression analysis. In terms of the functions of SERPINE1, the results of enrichment analysis indicated that SERPINE1 was mainly enriched in the immune‐related biological processes and signaling pathways. Furthermore, it was closely associated with infiltrations of immune cells in the LGG microenvironment and acted synergistically with PD1, PD-L1, PD-L2.ConclusionThese findings proved that SERPINE1 could serve as a prognostic biomarker and potential immunotherapy target of LGGs.

scholarly journals Prognostic Stratification for IDH-wild-type Lower-grade Astrocytoma by Sanger Sequencing and Copy-number Variation Analysis with MLPA.

2021 ◽  
Author(s):  
Yasuhide Makino ◽  
Yoshiki Arakawa ◽  
Ema Yoshioka ◽  
Tomoko Shofuda ◽  
Takeshi Kawauchi ◽  
...  
Keyword(s):  
Copy Number ◽  
Sanger Sequencing ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Copy Number Variations ◽  
University Hospital ◽  
Prognostic Indicators ◽  
Lower Grade ◽  
Wild Type ◽  
Who Grade

Abstract The characteristics of IDH-wild-type lower-grade astrocytoma remain unclear. According to cIMPACT-NOW update 3, IDH-wild-type astrocytomas with any of the following factors show poor prognosis: combination of chromosome 7 gain and 10 loss (+ 7/-10), and/or EGFR amplification, and/or TERT promoter (TERTp) mutation. Multiplex ligation-dependent probe amplification (MLPA) can detect copy number variations with a reasonable cost. The purpose of this study was to find precise and cost-effective method for stratifying the prognosis of IDH-wild-type astrocytomas. Sanger sequencing, MLPA, and quantitative methylation-specific PCR were performed for 42 IDH-wild-type lower-grade astrocytomas surgically treated at Kyoto University Hospital, and overall survival was analyzed for 40 patients who underwent first surgery. Of the 42 IDH-wild-type astrocytomas, 21 were classified as grade 4 in cIMPACT-NOW update 3 criteria and all of them had either TERTp mutation or EGFR amplification. Kaplan-Meier analysis confirmed the prognostic significance of cIMPACT-NOW criteria, and WHO grade was also prognostic. Cox regression hazard model identified PTEN loss and PDGFRA amplification as independent significant prognostic indicators (Risk ratio of 9.75, p < 0.001 and 13.9, p = 0.002). The classification recommended by cIMPACT-NOW update 3 could be completed using Sanger sequencing and MLPA. Survival analysis revealed PTEN and PDGFRA were significant prognostic factors for IDH-wild-type lower-grade astrocytoma.

scholarly journals MYD88 Is a Potential Prognostic Gene and Immune Signature of Tumor Microenvironment for Gliomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Qinglong Guo ◽  
Xing Xiao ◽  
Jinsen Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Cox Regression ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Clinical Cases

PurposeTo explore the profiles of immune and stromal components of the tumor microenvironment (TME) and their related key genes in gliomas.MethodsWe applied bioinformatic techniques to identify the core gene that participated in the regulation of the TME of the gliomas. And immunohistochemistry staining was used to calculate the gene expressions in clinical cases.ResultsThe CIBERSORT and ESTIMATE were used to figure out the composition of TME in 698 glioma cases from The Cancer Genome Atlas (TCGA) database. Differential expression analysis identified 2103 genes between the high and the low-score group. Then the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, univariate Cox regression analysis, and protein–protein interaction (PPI) network construction were conducted based on these genes. MYD88 was identified as the key gene by the combination univariate Cox and PPI analysis. Furthermore, MYD88 expression was significantly associated with the overall survival and WHO grade of glioma patients. The genes in the high-expression MYD88 group were mainly in immune-related pathways in the Gene Set Enrichment Analysis (GSEA). We found that macrophage M2 accounted for the largest portion with an average of 27.6% in the glioma TIICs and was associated with high expression of MYD88. The results were verified in CGGA database and clinical cases in our hospital. Furthermore, we also found the MYD88 expression was higher in IDH1 wild types. The methylation rate was lower in high grade gliomas.ConclusionMYD88 had predictive prognostic value in glioma patients by influencing TIICs dysregulation especially the M2-type macrophages.

scholarly journals PATH-37. PROGNOSTIC ROLE OF TERT PROMOTER MUTATIONS IMPROVES THE STRATIFICATION OF IDH-MUTATED LOWER GRADE GLIOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi151-vi151
Author(s):  
Hideyuki Arita ◽  
Yuko Matsushita ◽  
Makoto Ohno ◽  
Yohei Miyake ◽  
Kuniaki Saito ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Molecular Diagnostic ◽  
Lower Grade ◽  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Tert Promoter ◽  
Grade Ii

Abstract TERT promoter mutation is associated with 1p/19q codeletion and favorable prognosis in IDH-mutated gliomas. Prognostic and diagnostic significance of TERT promoter mutation is well-recognized in IDH-wildtype glioblastomas, but not in IDH-mutated gliomas. We investigated prognostic efficacy of TERT mutation in a cohort of 560 Japanese IDH-mutated adult gliomas. The molecular status of IDH, TERT and 1p/19q and patient clinical data including Karnofsky performance status (KPS) were collected in all cases. TERT mutations and 1p/19q codeletions were found in 303 and 285 cases, respectively. The patient cohort was divided into four groups by a combination of the 1p/19q and TERT status. The characteristics of 1p/19q intact-TERT mutated group (Astro-TERT group, n=24) were compared with those of 1p/19q intact-TERT wild (Astro-group, n=251) or 1p/19q codeleted-TERT mutated (Oligo-group, n=279) cases. Astro-TERT group with any grade showed intermediate overall survival between the Oligo-group and Astro-group although the survival differences were not statistically significant (median overall survival (OS) not reached (NR) versus NR, and 106 months, respectively. p >0.05). We further conducted subgroup analysis by adjusting KPS and WHO grade as Cox regression analysis for survival indicated the unfavorable survival impact of KPS < 90 and WHO grade IV. In the subgroup with favorable KPS (90–100) and grade II-III (n=438), The OS of Astro-TERT group (median NR) was significantly longer survival than that of Astro-group (median 120.2 months, p=0.032), and was comparable with that of the Oligo-group (median NR, p >0.05). On the other hand, OS of none of the molecular groups significantly differ in poorer KPS subgroups (p >0.05). In grade IV tumors, the OS of the Astro-TERT group (NR) was comparable with that of Astro-group (29 months, p=0.19) rather than Oligo-group (NR, p=0.051). Thus, TERT promoter status provides a valuable prognostic information for IDH-mutated grade II-III gliomas in the current molecular diagnostic system.

scholarly journals Soluble urokinase-type plasminogen activator receptor (suPAR) is a risk indicator for eGFR loss in kidney transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ulrich Jehn ◽  
Katharina Schütte-Nütgen ◽  
Ute Henke ◽  
Hermann Pavenstädt ◽  
Barbara Suwelack ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Cox Regression ◽  
Kidney Diseases ◽  
Prognostic Significance ◽  
Risk Indicator ◽  
Kidney Transplant Recipients ◽  
Supar Level ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
One Year

AbstractThe prognostic significance of suPAR in various kidney diseases has recently been demonstrated. Its role in transplantation-specific outcomes is still largely unknown. Therefore, we prospectively investigated the prognostic relevance of suPAR in patients before and one year after kidney transplantation (KTx). We included 100 patients who had received a kidney transplantation between 2013 and 2015. The plasma concentration of suPAR was measured by ELISA assay. In recipients of living donations (LD), pre-transplant suPAR levels were significantly lower than those of recipients of deceased donations (DD). After KTx, suPAR levels significantly declined in LD and DD recipients, without a detectable difference between both groups any more. Higher suPAR levels in recipients one year after KTx were associated with a more severe eGFR loss in the following three years in multivariable cox-regression (n = 82, p = 0.021). suPAR-levels above 6212 pg/ml one year after KTx are associated with eGFR loss > 30%, which occurred almost twice as fast as in patients with suPAR ≤ 6212 pg/ml (p < 0.001). Hence, suPAR level at one year mark might be a risk indicator of increased eGFR loss.

scholarly journals Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

2021 ◽  
Vol 12 (1) ◽  
pp. 67-75
Author(s):  
Ying Yang ◽  
Jin Wang ◽  
Shihai Xu ◽  
Fei Shi ◽  
Aijun Shan
Keyword(s):  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Gliomas ◽  
Strongly Correlated ◽  
Who Grade ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
R Language ◽  
Biological Adhesion ◽  
Tcga Dataset

Abstract Background Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. Methods Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses. Results CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age. Conclusions CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.

scholarly journals The expression of miR-211-5p in atherosclerosis and its influence on diagnosis and prognosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanxia Zhang ◽  
Huiyun Wang ◽  
Yu Xia
Keyword(s):  
Roc Curve ◽  
Cox Regression ◽  
Survival Curve ◽  
Prognostic Significance ◽  
Significant Negative Correlation ◽  
Diagnostic Value ◽  
Expression Level ◽  
Healthy Controls ◽  
Cox Regression Analysis ◽  
Diagnosis And Prognosis

Abstract Background The purpose of this study was to evaluate the diagnostic and prognostic significance of miR-211-5p in atherosclerosis (AS) by detecting the expression level in serum of patients with AS. Methods A total of 85 healthy controls and 90 asymptomatic AS patients participated in this study. The expression level of miR-211-5p in all subjects were measured by qRT-PCR. Spearman correlation coefficient was used to evaluate the correlation of miR-211-5p with CRP and CIMT. The ROC curve was established to assess the diagnostic value of miR-211-5p in AS. The Kaplan–Meier survival curve and multivariate COX regression analysis were used to evaluate the prognostic significance of miR-211-5p in AS. Results The expression levels of miR-211-5p in AS patients were significantly lower than in healthy controls (P < 0.001), and miR-211-5p showed a significant negative correlation with CRP (r =  − 0.639, P < 0.001) and CIMT (r =  − 0.730, P < 0.001). The AUC of the ROC curve was 0.900, the specificity and the sensitivity were 84.7% and 78.9%, respectively, which indicating that miR-211-5p had diagnostic value for AS. Survival analysis showed that patients with low miR-211-5p expression were more likely to have cardiovascular end-point events (Log rank P = 0.013). Conclusion Serum miR-211-5p could be used as a new biomarker for the diagnosis of AS, and the low expression of miR-211-5p is associated with the poor prognosis of AS.

The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽  
2021 ◽  
Author(s):  
Peng Wang ◽  
Chen Luo ◽  
Peng-jie Hong ◽  
Wen-ting Rui ◽  
Shuai Wu
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Lower Grade ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

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