scholarly journals A pan-cancer perspective analysis reveals the opposite prognostic significance of CD133 in lower grade glioma and papillary renal cell carcinoma

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110109
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Prognostic Factor ◽  
Prognostic Significance ◽  
Papillary Renal Cell Carcinoma ◽  
High Expression ◽  
Lower Grade ◽  
Cd133 Expression ◽  
The Poor ◽  
Lower Grade Glioma ◽  
Pan Cancer ◽  
Perspective Analysis

CD133 is a valuable prognostic marker in multiple types of cancer. However, the expression, methylation levels, and prognostic relevance of CD133 have not been evaluated in a pan-cancer perspective. The expression and methylation levels of CD133 across different types of cancer were determined using The Cancer Genome Atlas (TCGA) dataset. Univariate cox regression and Kaplan-Meier survival were used to determine the prognostic significance of CD133 expression and methylation. CD133 was highly expressed in papillary renal cell carcinoma (PRCC) or pancreatic adenocarcinoma (PAAD). Correspondingly, PAAD and PRCC had low CD133 methylation levels. Through pan-cancer perspective analysis, we found that CD133 high expression was a poor prognostic factor in lower grade glioma (LGG), while, CD133 high expression was a good prognostic factor in PRCC. Moreover, genes positively correlated with CD133 expression were associated with the poor clinical outcomes of LGG. In PRCC, genes negatively correlated with CD133 expression were correlated with the poor overall survival. Furthermore, CD133 expression levels were highly correlated with the CD133 methylation levels in LGG or PRCC. Correspondingly, CD133 hypermethylation was a good prognostic factor in LGG. On the contrary, CD133 hypomethylation was a good prognostic factor in PRCC. We also found that CD133 was highly expressed and hypomethylated in wild type IDH subgroup of LGG. CD133 was highly expressed and hypomethylated in low stages and type1 of PRCC. CD133 high expression and hypomethylation were bad prognostic factors in LGG, while, CD133 high expression and hypomethylation were good prognostic factors in PRCC.

scholarly journals Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Huaide Qiu ◽  
Wei Tian ◽  
Yikang He ◽  
Jiahui Li ◽  
Chuan He ◽  
...  
Keyword(s):  
Immune Response ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Prognostic Value ◽  
Integrated Analysis ◽  
Lower Grade ◽  
Qrt Pcr ◽  
Lower Grade Glioma ◽  
Pan Cancer ◽  
Genome Atlas

BackgroundCD86 has great potential to be a new target of immunotherapy by regulating cancer immune response. However, it remains unclear whether CD86 is a friend or foe in lower-grade glioma (LGG).MethodsThe prognostic value of CD86 expression in pan-cancer was analyzed using Cox regression and Kaplan-Meier analysis with data from the cancer genome atlas (TCGA). Cancer types where CD86 showed prognostic value in overall survival and disease-specific survival were identified for further analyses. The Chinese Glioma Genome Atlas (CGGA) dataset were utilized for external validation. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and Immunohistochemistry (IHC) were conducted for further validation using surgical samples from Jiangsu Province hospital. The correlations between CD86 expression and tumor immunity were analyzed using the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, Tumor IMmune Estimation Resource (TIMER) database, and expressions of immune checkpoint molecules. Gene Set Enrichment Analysis (GSEA) was performed using clusterprofiler r package to reveal potential pathways.ResultsPan-cancer survival analysis established CD86 expression as an unfavorable prognostic factor in tumor progression and survival for LGG. CD86 expression between Grade-II and Grade-III LGG was validated using qRT-PCR and WB. Additionally, CD86 expression in LGG with unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter was significantly higher than those with methylated MGMT (P<0.05), while in LGG with codeletion of 1p/19q it was significantly downregulated as opposed to those with non-codeletion (P<2.2*10-16). IHC staining validated that CD86 expression was correlated with MGMT status and X1p/19q subtypes, which was independent of tumor grade. Multivariate regression validated that CD86 expression acts as an unfavorable prognostic factor independent of clinicopathological factors in overall survival of LGG patients. Analysis of tumor immunity and GSEA revealed pivotal role of CD86 in immune response for LGG.ConclusionsIntegrated analysis shows that CD86 is an unfavorable prognostic biomarker in LGG patients. Targeting CD86 may become a novel approach for immunotherapy of LGG.

scholarly journals A Pan-Cancer Analysis of Clinical Prognosis and Immune Infiltration of CKS1B in Human Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Yan Jia ◽  
Quan Tian ◽  
Kaitai Yang ◽  
Yi Liu ◽  
Yanfeng Liu
Keyword(s):  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Scale ◽  
Lower Grade ◽  
Clinical Prognosis ◽  
Bladder Urothelial Carcinoma ◽  
Lower Grade Glioma ◽  
Infiltrating Lymphocytes ◽  
First Time ◽  
Pan Cancer

Although more and more evidence supports CDC28 protein kinase subunit 1B (CKS1B) is involved significantly in the development of human cancers, most of the researches have focused on a single disease, and pan-cancer studies conducted from a holistic perspective of different tumor sources have not been reported yet. Here, for the first time, we investigated the potential oncogenic and prognostic role of CKS1B across 33 tumors based on public databases and further verified it in a small scale by RNA sequencing or quantitative real-time PCR. CKS1B was generally highly expressed in a majority of tumors and had a notable correlation with the prognosis of patients, but its prognostic significance in different tumors was not exactly the same. In addition, CKS1B expression was also closely related to the infiltration of cancer-associated fibroblasts in tumors such as breast invasive carcinoma, kidney chromophobe, lung adenocarcinoma, and tumor-infiltrating lymphocytes in tumors such as glioblastoma multiforme, bladder urothelial carcinoma, and brain lower grade glioma. Moreover, reduced CKS1B methylation was observed in certain tumors, for example, adrenocortical carcinoma. Cell cycle and kinase activity regulation and PI3K-Akt signaling pathway were found to be involved in the functional mechanism of CKS1B. In conclusion, our first pan-cancer analysis of CKS1B contributes to a better overall understanding of CKS1B and may provide a new target for future cancer therapy.

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 MPC-06 LRG1 HAS MULTIPLE POTENTIAL FOR CLINICOPATHOLOGICAL BIOMARKER OF GLIOBLASTOMA

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii23-ii23
Author(s):  
Takuya Furuta ◽  
Yasuo Sugita ◽  
Satoru Komaki ◽  
Kouichi Ohshima ◽  
Motohiro Morioka ◽  
...  
Keyword(s):  
Extent Of Resection ◽  
Tumor Location ◽  
High Expression ◽  
Karnofsky Performance Scale ◽  
Lower Grade ◽  
Diffuse Glioma ◽  
Tumor Tissues ◽  
Lower Grade Glioma ◽  
Expression Rate ◽  
Tumor Types

Abstract BACKGROUND AND AIM Leucine-rich α-2 glycoprotein 1 (LRG1) is one of the candidate proteins as a diagnostic marker for glioblastoma. Although association with angiogenesis has been reported, it has been suggested that the role as a biomarker differs depending on the tumor types. The role of LRG1 as a biomarker in glioblastoma was examined clinicopathologically. METHODS Tumor tissues of 156 cases diagnosed as diffuse glioma (27 astrocytomas, 15 oligodendrogliomas, 114 glioblastomas) according to WHO 2016 classification at Kurume University from January 2001 to April 2019 were used. The immunohistochemical intensity of LRG1 was scoring as 4 stages and classified into 2 groups; score 0–1 was defined as low expression and score 2–3 was defined as high expression. Mutations of IDH1/2 and TERT promoter were analyzed by Sanger method. In glioblastoma, the relationship between LRG1 expression and clinical parameters such as age, preoperative Karnofsky Performance Scale, tumor location, extent of resection, MGMT promoter, and prognosis were examined. RESULTS LRG1 high expression rate was 41.2% (47/114) in glioblastoma, 3.7% (1/27) in astrocytoma, 20% (3/15) in oligodendroglioma, and glioblastoma showed significant higher expression level of LRG1 compared with lower-grade glioma (p = 0.0003). High expression of LRG1 was an independent favorable prognostic factor (HR 0.41, 95% CI 0.18–0.86, p=0.019) in IDH-wildtype glioblastoma, and correlated with gross total resection (p = 0.002) and the tumor location of the non-subventricular zone (SVZ) (p = 0.00007). CONCLUSION LRG1 demonstrated multiple potential as diagnostic, prognostic, and regional biomarker for glioblastoma.

scholarly journals Transcriptomic Analysis of Glioma Based on IDH Status Identifies ACAA2 as a Prognostic Factor in Lower Grade Glioma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Chenxing Wu ◽  
Hongwang Song ◽  
Xiaojun Fu ◽  
Shouwei Li ◽  
Tao Jiang
Keyword(s):  
Prognostic Factor ◽  
Network Analysis ◽  
Targeted Therapies ◽  
Correlation Network ◽  
Lower Grade ◽  
Gene Expressions ◽  
Who Grade ◽  
Lower Grade Glioma ◽  
Idh Mutations ◽  
Weighted Correlation

Background. Glioma is the most common and lethal tumor in the central nervous system (CNS). More than 70% of WHO grade II/III gliomas were found to harbor isocitrate dehydrogenase (IDH) mutations which generated targetable metabolic vulnerabilities. Focusing on the metabolic vulnerabilities, some targeted therapies, such as NAMPT, have shown significant effects in preclinical and clinical trials. Methods. We explored the TCGA as well as CGGA database and analyzed the RNA-seq data of lower grade gliomas (LGG) with the method of weighted correlation network analysis (WGCNA). Differential expressed genes were screened, and coexpression relationships were grouped together by performing average linkage hierarchical clustering on the topological overlap. Clinical data were used to conduct Kaplan–Meier analysis. Results. In this study, we identified ACAA2 as a prognostic factor in IDH mutation lower grade glioma with the method of weighted correlation network analysis (WGCNA). The difference of ACAA2 gene expressions between the IDH wild-type (IDH-WT) group and the IDH mutant (IDH-MUT) group suggested that there may be different potential targeted therapies based on the fatty acid metabolic vulnerabilities, which promoted the personalized treatment for LGG patients.

Tumor Mutational Burden and Survival in Papillary Renal Cell Carcinoma Patients

2021 ◽  
Author(s):  
Haiyang Ding ◽  
Shu Yan ◽  
Yuying Han ◽  
Zhenguo Ji ◽  
Peiqian Yang
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Immune Cell ◽  
Papillary Renal Cell Carcinoma ◽  
High Expression ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Checkpoint Genes

Abstract Background: Papillary renal cell carcinoma (PRCC) is the second most prevalent subtype of renal cell carcinoma (RCC), accounting for 15% of all RCCs. Tumor mutational burden (TMB) is a promising prognostic factor in many types of cancers. The present study aimed to investigate the association between TMB and patient survival in PRCC patients.Methods: Genomic and clinical data of 281 PRCC patients were collected from The Cancer Genome Atlas. Overall survival (OS) was compared between patients with high and low TMB using the Kaplan-Meier method with log-rank tests. Gene expression comparison and immune cell fraction comparison were performed using Student’s t test or Wilcoxon’s rank-sum test. Results: Patients with high TMB tumors had longer OS than those with low TMB tumors. Among tumor-infiltrating immune cells, high TMB tumors were associated with high levels of CD4+ T-cell infiltration, which were further associated with better survival. Furthermore, low TMB tumors were associated with a high level of infiltration of regulatory T-cells and dendritic cells. Among immune checkpoint genes, low TMB tumors expressed high levels of CD274, PDCD1LG2, LAG3, and TGFB1, and these genes were associated with a poor prognosis in PRCC. Among cytokine-related genes, low TMB tumors were associated with a high expression of IL6, whereas high TMB tumors were associated with a high expression of IFNA1.Conclusions: High TMB indicated better survival outcomes in PRCC patients. High TMB was associated with anti-tumor immune cell infiltration, whereas low TMB was associated with high expression of checkpoint genes that indicated a worse prognosis in RCC. Moreover, TMB was associated with the expression of immune cytokines. Thus, TMB may be a novel prognostic factor in PRCC.

scholarly journals Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 967
Author(s):  
María I. Aroca-Siendones ◽  
Sara Moreno-SanJuan ◽  
Jose D. Puentes-Pardo ◽  
Michela Verbeni ◽  
Javier Arnedo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Prognostic Significance ◽  
Developed Countries ◽  
Disease Diagnosis ◽  
Independent Prognostic Factor ◽  
High Expression ◽  
Incidence And Mortality ◽  
Circadian Clock Proteins ◽  
Low Expression

Colorectal cancer (CRC) is one of the most common tumours in developed countries. Although its incidence and mortality rates have decreased, its prognosis has not changed, and a high percentage of patients with CRC develop relapse (metachronous metastasis, MM, or local recurrence, LR) during their disease. The identification of these patients is very important for their correct management, but the lack of prognostic markers makes it difficult. Given the connection between circadian disruption and cancer development and progression, we aimed to analyse the prognostic significance of core circadian proteins in CRC. We measured the expression of PER1-3, CRY1-2, BMAL1 and NR1D2 in a cohort of CRC patients by immunohistochemistry (IHC) and analysed their prognostic potential in this disease. A low expression of PER2 and BMAL1 was significantly associated with metastasis at the moment of disease diagnosis, whereas a high expression of CRY1 appeared as an independent prognostic factor of MM development. A high expression of NR1D2 appeared as an independent prognostic factor of LR development after disease diagnosis. Moreover, patients with a low expression of BMAL1 and a high expression of CRY1 showed lower OS and DFS at five years. Although these markers need to be validated in larger and different ethnic cohorts, the simplicity of IHC makes these proteins candidates for personalizing CRC treatment.

scholarly journals GPX7 is Identified as a Novel Prognostic Indicator for Brain Lower Grade Glioma (LGG): Evidence from a Pan-Cancer Analysis

2021 ◽  
Author(s):  
Qianqian Zhao ◽  
Yin Yang ◽  
Luyu Zhang ◽  
Yingying Wang ◽  
Tianpei Wang ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Poor Prognosis ◽  
Enrichment Analysis ◽  
Prognostic Indicator ◽  
Lower Grade ◽  
Free Survival ◽  
Multiple Tumors ◽  
Expression Levels ◽  
Lower Grade Glioma ◽  
Pan Cancer

Abstract Background: Glutathione peroxidase-7 (GPX7), a newly discovered non-selenium-containing protein with glutathione peroxidase activity, is located near the endoplasmic reticulum. Various studies have reported the involvement of GPX7 in cancer disease progression. However, the expression patterns of GPX7 and its prognostic potential have not been evaluated from a pan-cancer perspective. Moreover, the relationship between GPX7 and prognosis in Brain Lower Grade Glioma (LGG) patients remains unclear.Methods: Expression levels of GPX7 were evaluated using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA2) were used to evaluate the effect of GPX7 on clinical prognosis in TCGA tumors. Correlations between GPX7 and cancer immune infiltrates were investigated using the Tumor Immune Estimation Resource (TIMER) site and Estimating the Proportions of Immune and Cancer cells (EPIC) algorithm. In addition, the GEPIA2 and STRING websites were used for enrichment analysis of GPX7-related genes. Finally, we constructed a prognostic Nomogram for LGG to verify the overall survival (OS) outcomes of patients.Results: GPX7 was found to be overexpressed in multiple tumors. Elevated expression levels of GPX7 were associated with poor prognosis regarding OS, disease-free survival (DFS) and progression-free survival (PFS) of LGG patients (OS Hazard ratio (HR) = 1.044, p < 0.0001; DFS HR = 1.035, p < 0.0001; PFS HR = 1.045, p < 0.0001). Concordance index (C-index) of the nomogram for LGG was 0.845 (95% CI, 0.825 to 0.865; p < 0.001). The nomogram exhibited a better predictability. In addition, GPX7 expression and the abundance of Cancer-associated fibroblasts (CAFs) were positively correlated in most cancer types. Enrichment analysis revealed that GPX7 may be involved in the glutathione derivative biosynthetic and glutathione metabolic biological processes.Conclusion: GPX7 was found to be upregulated in multiple tumors, which was correlated with poor prognosis in LGG. Therefore, GPX7 is a potential prognostic indicator for LGG. There is a strong correlation between GPX7 expression levels and glutathione metabolic pathways. GPX7 holds promise for the use of glutathione metabolism for guided therapy in cancer patients.

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