scholarly journals Overexpressed XRCC2 as an independent risk factor for poor prognosis in glioma patients

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Zhendong Liu ◽  
Wang Zhang ◽  
Xingbo Cheng ◽  
Hongbo Wang ◽  
Lu Bian ◽  
...  
Keyword(s):  
Risk Factor ◽  
Expression Pattern ◽  
Poor Prognosis ◽  
Independent Risk Factor ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Cellular Mechanisms ◽  
Molecular Features ◽  
Meta Analyses

Abstract Background XRCC2, a homologous recombination-related gene, has been reported to be associated with a variety of cancers. However, its role in glioma has not been reported. This study aimed to find out the role of XRCC2 in glioma and reveal in which glioma-specific biological processes is XRCC2 involved based on thousands of glioma samples, thereby, providing a new perspective in the treatment and prognostic evaluation of glioma. Methods The expression characteristics of XRCC2 in thousands of glioma samples from CGGA and TCGA databases were comprehensively analyzed. Wilcox or Kruskal test was used to analyze the expression pattern of XRCC2 in gliomas with different clinical and molecular features. The effect of XRCC2 on the prognosis of glioma patients was explored by Kaplan–Meier and Cox regression. Gene set enrichment analysis (GSEA) revealed the possible cellular mechanisms involved in XRCC2 in glioma. Connectivity map (CMap) was used to screen small molecule drugs targeting XRCC2 and the expression levels of XRCC2 were verified in glioma cells and tissues by RT-qPCR and immunohistochemical staining. Results We found the overexpression of XRCC2 in glioma. Moreover, the overexpressed XRCC2 was associated with a variety of clinical features related to prognosis. Cox and meta-analyses showed that XRCC2 is an independent risk factor for the poor prognosis of glioma. Furthermore, the results of GSEA indicated that overexpressed XRCC2 could promote malignant progression through involved signaling pathways, such as in the cell cycle. Finally, doxazosin, quinostatin, canavanine, and chrysin were identified to exert anti-glioma effects by targeting XRCC2. Conclusions This study analyzed the expression pattern of XRCC2 in gliomas and its relationship with prognosis using multiple datasets. This is the first study to show that XRCC2, a novel oncogene, is significantly overexpressed in glioma and can lead to poor prognosis in glioma patients. XRCC2 could serve as a new biomarker for glioma diagnosis, treatment, and prognosis evaluation, thus bringing new insight into the management of glioma.

scholarly journals Identification of AC003986.3 as an Independent Risk Factor for Glioma Patient Survival and Functional Analysis

2020 ◽  
Author(s):  
Qinglin Liu ◽  
Huijian Ge ◽  
Peng Jiang
Keyword(s):  
Risk Factor ◽  
Clinical Features ◽  
Independent Risk Factor ◽  
Cox Regression ◽  
Patient Survival ◽  
Cell Metabolism ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Pathological Grade ◽  
Gene Sets

Abstract Background: To validate the potential of AC003986.3 in predicting glioma patient survival and analyze its underlying mechanism.Methods: Gene expression and clinical features of the patients with gliomas were obtained from The Cancer Genome Atlatls. Correlation between AC003986.3 expression profile and patient clinical features and survival were analyzed. Multivariate Cox regression was employed to determine the risk factors for patient survival and construct the prediction model for survival. Validation of the multivariate Cox regression model was performed by comparing the survival curves between the model-predicted high and low death risk subgroups and calculating the accuracy of predicting 1, 2, 3, and 5 years survival by the model. Target genes were predicted with Ensemble Browser. Gene set enrichment analysis was performed to explore AC003986.3 related gene sets enrichment in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways.Results: 655 samples with gene expression and complete clinical features were obtained from The Cancer Genome Atlas. Clinical features enrolled in this study were follow up time, survival status, race, gender, race and pathological grade. AC003986.3 expression was positively related to patient age and pathological grade. Patients with High AC003986.3 expression suffered a poorer survival than those with low expression. Multivariate Cox regression revealed that AC003986.3 expression was an independent risk factor for patient survival irrespective of age and pathological grade. Predicted by Ensemble Browser, TWIST1 was identified as the target of AC003986.3. Gene set enrichment analysis revealed that AC003986.3 related gene sets were mainly enriched in cell metabolism.Conclusions: AC003986.3 expression was closely related to age and pathological grade in glioma patients, and was an independent risk factor for patient survival irrespective of age and pathological grade. AC003986.3 was mainly involved in regulating tumor cell metabolism, and this effect is probably mediated by TWIST1.

scholarly journals Abnormal TACC3 Expression is an Independent Prognostic Biomarker in Lung Carcinoma

2020 ◽  
Author(s):  
Dongwei He ◽  
Xiaoyan Fan ◽  
Yulong Zhang ◽  
You Li
Keyword(s):  
Risk Factor ◽  
Lung Carcinoma ◽  
Independent Risk Factor ◽  
Cox Regression ◽  
Coiled Coil ◽  
Enrichment Analysis ◽  
Diagnostic Value ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Roc Curve Analysis

Abstract Background: Abnormal expression of transforming acidic coiled-coil protein 3 (TACC3) correlates with tumorigenesis of many human malignancies. However, the expression pattern of TACC3 and its clinical significance have not been well characterized in lung carcinoma (LUAD) so far. Objective: To investigate the association of TACC3 expression level with the clinicopathological characteristics and prognosis of LUAD patients.Methods: In the study, based on Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and The Cancer Genome Atlas (TCGA) databases, the expression of TACC3 was determined in LUAD patients. Further, the expression of TACC3 was established using qRT-PCR in LUAD patients. Results: Our results showed that TACC3 was significantly overexpressed in LUAD tumors compared with non-tumors in the above public databases (all p<0.01). A receiver operating characteristic (ROC) curve analysis suggested that TACC3 may have diagnostic value in LUAD patients (normal vs tumor: AUC = 0.940). Kaplan-Meier analysis further demonstrated that high TACC3 expression in tumors was significantly associated with worse overall survival (OS) in LUAD patients (all p<0.01). In addition, Univariate and multivariate Cox regression analyses showed that TACC3 was an independent risk factor for OS among LUAD patients (HR = 1.02, 95% CI: 1.01-1.04, p = 0.00823; HR=1.43, 95% CI: 1.17-1.70, p <0.001). Finally, using gene set enrichment analysis (GSEA 3.0), we found that a series of potential pathways related to TACC3 were highly enriched with the high TACC3 expression phenotype (p = 0.024, p = 0.003, respectively). Conclusions: The present study provides evidence that TACC3 expression is upregulated in tumors and may be an independent risk factor for prognosis in LUAD patients.

scholarly journals Identification of AC003986.3 as an independent risk factor for glioma patient survival and functional analysis

2020 ◽  
Author(s):  
Qinglin Liu ◽  
Huijian Ge ◽  
Peng Liu ◽  
Youxiang Li ◽  
Peng Jiang
Keyword(s):  
Risk Factor ◽  
Clinical Features ◽  
Independent Risk Factor ◽  
Cox Regression ◽  
Patient Survival ◽  
Cell Metabolism ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Pathological Grade ◽  
Gene Sets

Abstract Background To validate the potential of AC003986.3 in predicting glioma patient survival and analyze its underlying function and mechanism. Methods Gene expression and clinical features of the patients were obtained from The Cancer Genome Atlatls. Correlation between AC003986.3 expression profile and patient clinical features and survival were analyzed. Multivariate Cox regression was employed to determine the risk factors for patient survival and construct the prediction model for survival. Validation of the multivariate Cox regression model was tested by comparing the survival curves between the model-predicted high and low death risk subgroups and calculating the accuracy of predicting 1, 2, 3, and 5 years survival by the model. Target genes were predicted with Ensemble Browser. Gene set enrichment analysis was performed to explore AC003986.3 related gene sets enrichment in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Results 655 samples with gene expression and complete clinical features were obtained from The Cancer Genome Atlas. Clinical features enrolled in this study were follow up time, survival status, race, gender, race and pathological grade. AC003986.3 expression was positively related to patient age and pathological grade. High AC003986.3 expression glioma patients suffered a poorer survival than those with low expression. Multivariate Cox regression revealed that AC003986.3 expression was an independent risk factor for patient survival irrespective of age and pathological grade. Predicted by Ensemble Browser, TWIST1 was the target of AC003986.3. Gene set enrichment analysis revealed that AC003986.3 related gene sets were mainly enriched in cell metabolism. Conclusions AC003986.3 expression is closely related to age and pathological grade in glioma patients, and is an independent risk factor for patient survival irrespective of age and pathological grade. AC003986.3 is mainly involved in regulating tumor cell metabolism, and this effect is probably mediated by TWIST1.

scholarly journals CKAP2L, as an Independent Risk Factor, Closely Related to the Prognosis of Glioma

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Li Zhu ◽  
Yanlei Zheng ◽  
Ronghua Hu ◽  
Chenchen Hu
Keyword(s):  
Cell Cycle ◽  
Risk Factor ◽  
Independent Risk Factor ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Biological Behavior ◽  
Therapeutic Effects ◽  
Cox Regression Analysis

Recent studies have found that cytoskeleton-associated protein 2 like (CKAP2L), an important oncogene, is involved in the biological behavior of many malignant tumors, but its function in the malignant course of glioma has not been confirmed. The main purpose of this study was to clarify the relationship between prognostic clinical characteristics of glioma patients and CKAP2L expression using data collected from the GEPIA, HPA, CGGA, TCGA, and GEO databases. CKAP2L expression was significantly increased in glioma. Further, Kaplan-Meier plots revealed that increased expression of CKAP2L was associated with shorter survival time of glioma patients in datasets retrieved from multiple databases. Cox regression analysis indicated that CKAP2L can serve as an independent risk factor but also has relatively reliable diagnostic value for the prognosis of glioma patients. The results of gene set enrichment analysis suggested that CKAP2L may play a regulatory role through the cell cycle, homologous recombination, and N-glycan biosynthesis cell signaling pathways. Several drugs with potential inhibitory effects on CKAP2L were identified in the CMap database that may have therapeutic effects on glioma. Finally, knockdown of CKAP2L inhibited the proliferation and invasion of cells by reducing the expression level of cell cycle-related proteins. This is the first study to demonstrate that high CKAP2L expression leads to poor prognosis in glioma patients, providing a novel target for diagnosis and treatment of glioma.

scholarly journals Overexpression of SKA3 correlates with poor prognosis in female early breast cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12506
Author(s):  
Yue Zhong ◽  
Zhenjie Zhuang ◽  
Peiju Mo ◽  
Mandi Lin ◽  
Jiaqian Gong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Molecular Subtype ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Chi Square ◽  
Exact Test ◽  
Chi Square Test

Background Spindle and kinetochore associated complex subunit 3 (SKA3) plays an important role in tumorigenesis and the progression of various tumors. But the relationship between SKA3 and early breast cancer remains unclear. The study aimed to explore the prognostic significance of SKA3 in breast cancer. Methods In the study, SKA3 expression was initially assessed using the Oncomine database and The Cancer Genome Atlas database (TCGA). Then, we presented validation results for RT-qPCR (quantitative reverse transcription PCR) and ELISA (enzyme-linked immunosorbent assay). The relationship between clinical characteristics and SKA3 expression was assessed by Chi-square test and Fisher’s exact test. Kaplan–Meier method and Cox regression analysis were conducted to evaluate the prognostic value of SKA3. Gene set enrichment analysis (GSEA) was performed to screen biological pathways using the TCGA dataset. Besides, single sample gene set enrichment analysis (ssGSEA) was utilized to identify immune infiltration cells about SKA3. Results SKA3 mRNA was expressed at high levels in breast cancer tissues compared with normal tissues. Chi-square test and Fisher’s exact test showed SKA3 expression was related to age, tumor (T) classification, node (N) classification, tumor-node-metastasis (TNM) stage, estrogen receptor (ER), progesterone receptor (PR), molecular subtype, and race. RT-qPCR results showed that SKA3 expression was overexpressed in ER, PR status, and molecular subtype in Chinese people. Kaplan–Meier curves implicated that high SKA3 expression was related to a poor prognosis in female early breast cancer patients. Cox regression models showed that high SKA3 expression could be used as an independent risk factor for female early breast cancer. Four signaling pathways were enriched in the high SKA3 expression group, including mTORC1 signaling pathway, MYC targets v1, mitotic spindle, estrogen response early. Besides, the SKA3 expression level was associate with infiltrating levels of activated CD4 T cells and eosinophils in breast cancer. Conclusion High SKA3 expression correlates with poor prognosis and immune infiltrates in breast cancer. SKA3 may become a biomarker for the prognosis of breast cancer.

scholarly journals Low UGP2 Expression Is Associated with Tumour Progression and Predicts Poor Prognosis in Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qiuyue Hu ◽  
Shen Shen ◽  
Jianhao Li ◽  
Liwen Liu ◽  
Xin Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Tumour Progression ◽  
Enrichment Analysis ◽  
Malignant Tumour ◽  
Diagnostic Value ◽  
Gene Set Enrichment Analysis ◽  
Uridine Diphosphate ◽  
Roc Curve Analysis

Hepatocellular carcinoma (HCC) is a malignant tumour associated with a high mortality rate and poor prognosis worldwide. Uridine diphosphate-glucose pyrophosphorylase 2 (UGP2), a key enzyme in glycogen biosynthesis, has been reported to be associated with the occurrence and development of various cancer types. However, its diagnostic value and prognostic value in HCC remain unclear. The present study observed that UGP2 expression was significantly downregulated at both the mRNA and protein levels in HCC tissues. Receiver operating characteristic (ROC) curve analysis revealed that UGP2 may be an indicator for the diagnosis of HCC. In addition, Kaplan-Meier and Cox regression multivariate analyses indicated that UGP2 is an independent prognostic factor of overall survival (OS) in patients with HCC. Furthermore, gene set enrichment analysis (GSEA) suggested that gene sets negatively correlated with the survival of HCC patients were enriched in the group with low UGP2 expression levels. More importantly, a significant correlation was identified between low UGP2 expression and fatty acid metabolism. In summary, the present study demonstrates that UGP2 may contribute to the progression of HCC, indicating a potential therapeutic target for HCC patients.

P6243Impact of coronary flow reserve as an important predictor for major adverse cardiac and cerebrovascular event in hemodialysis patients even in patients without myocardial perfusion abnormality

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Umemoto ◽  
S Ooshima ◽  
S Ooshima ◽  
R Itou ◽  
R Itou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Myocardial Perfusion ◽  
Coronary Flow ◽  
Poor Prognosis ◽  
Independent Risk Factor ◽  
Cox Regression ◽  
Cerebrovascular Event ◽  
Intergroup Difference ◽  
Flow Reserve

Abstract Background In the clinical setting, ischemic heart disease (IHD) is a major problem not only in general patients but also in regular hemodialysis (HD) patients. 13N-ammonia positron emission tomography (13NH3PET) is an established and excellent diagnostic test for IHD. We have reported about the predictability of coronary flow reserve (CFR) in poor prognosis in HD population. Some prior studies show that low CFR predicts poor prognosis for not only cardiovascular event but also all-cause mortality. Although it is well-known that CFR is an important predictor, there are limited data about CFR of patients without myocardial perfusion (MP) abnormality. We investigated the prognostic predictability of adverse cardiac and cerebrovascular event (MACCE) in HD patients without MP abnormality. Methods A total 438 of HD patients who underwent 13NH3PET for suspected IHD were enrolled. All patients were underwent 13NH3PET at our facility. After we excluded patients whose summed stress score (SSS) >3, we identified 182 eligible patients. Patients were divided into two group according to the median value of CFR; low CFR group (≤2.405) and high CFR group (>2.405). We followed up them up to 4.2 years (median 2.4 years) and collected their data. We evaluated their major adverse cardiac cerebrovascular event. We performed Kaplan-Meyer analysis and multivariable cox regression models. Furthermore, we evaluated the incremental value with C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) when CFR added into a model with established risk factors. Results There were intergroup difference in baseline characteristics: age, gender, prior CVD and diabetes. Kaplan-Meyer analysis shows statistically intergroup difference [log rank p=0.04, hazard ratio (HR) 0.54, 95% confidential interval (CI) 0.30–0.97]. Multivariable cox regression model for MACCE shows CFR is an independent risk factor (p=0.04, HR 0.54, 95% CI 0.30–0.97). As regarding model discrimination, all of C-index (0.82 vs 0.80, p=0.23), NRI (0.51, p<0.01) and IDI (0.03, p=0.03) were greatest in a predicting model with established risk factors plus CFR. Conclusions The low CFR group had poor prognosis in MACCE comparing to the high CFR group. CFR would be an independent risk factor for MACCE. Adding CFR on conventional risk factors could more accurately predict MACCE in HD patients, even in patients without MP abnormality.

scholarly journals Increased Expression Together with the Gene Regulation Network of NEIL3 Predicts Poor Prognosis and Correlates with Immune Infiltrates in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Bo Hu ◽  
Xiao-Bo Yang ◽  
Xinting Sang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Regulation ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Immune Gene ◽  
Data Set ◽  
Gene Markers

Abstract Background: Abnormal Nei endonuclease VIII-like 3 (NEIL3)expression is associated with carcinogenesis. Methods: We used sequencing data from the Cancer Genome Atlas database, analyzed NEIL3 expression, gene regulation networks and the correlation with immune infiltrates in hepatocellular carcinoma (HCC). Clinicopathologic characteristics associated with overall survival in TCGA patients using Cox regression and the Kaplan-Meier method. Gene Set Enrichment Analysis was performed using TCGA data set. LinkedOmics was used to identify differential gene expression with NEIL3 and to analyze Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Gene enrichment analysis examined target networks of kinases and transcription factors.Correlations between NEIL3 expression and cancer immune infiltrates and immune gene markers were analyzed by TIMER and GEPIA. Results: We found that overexpressed NEIL3 predicted poor prognosis. Functional network analysis suggested that NEIL3 regulates the DNA replication and cell cycle signaling via pathways involving several cancer-related kinases and E2F Transcription Factor 1.NEIL3 was also found to be associated with the infiltration of several immune cells. Conclusions: Our results demonstrate that data mining efficiently reveals information about NEIL3 expression, potential regulatory networks and the relationship with immune infiltration in HCC, laying a foundation for further study of the role of NEIL3 in carcinogenesis.

scholarly journals Low REST Expression Indicates a Biomarker of Poor Prognosis in Patients with Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chaoxiang Lv ◽  
Yuanguo Li ◽  
Qiqi Zhang ◽  
Yanyan Chen ◽  
Dandan Wei ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Cholesterol Homeostasis ◽  
Gene Set Enrichment Analysis ◽  
Cox Regression Analysis

It was initially found that neural-restrictive silencer factor/repressor 1-silencing transcription factor (REST) is a transcriptional repressor of neuronal genes in nonneuronal cells. However, it is reported to be abundantly expressed in various types of aggressive cancer cells. In this study, we evaluated the expression patterns of REST in renal cell carcinoma and found that its expression is lower in tumor tissues compared to normal tissues. The chi-square test showed that the low REST expression was closely related to patients’ clinicopathologic parameters, including the pathologic stage and survival status. ROC curve showed that REST had excellent clinical diagnostic prospect. In addition, patients with low REST expression had poor over survival (OS) and relapse-free survival (RFS). Univariate and multivariate Cox regression analysis confirmed that the low REST expression was an independent predictor of poor prognosis in renal cell carcinoma. Gene set enrichment analysis identified P53 pathway, reactive oxygen species pathway, glycolysis, DNA repair, cholesterol homeostasis, and MYC targets V2 enriched with low REST expression phenotype. These results suggested that REST may be a novel biomarker for the diagnosis and prognosis of renal cell carcinoma in clinical applications.

scholarly journals Retinoic acid metabolism-related enzyme signature identified prognostic and immunotherapeutic efficiency in sarcoma

2021 ◽  
Author(s):  
Huaiyuan Xu ◽  
JinXin Hu ◽  
YiJiang Song ◽  
HongMin Chen ◽  
YanYang Xu ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Acid Metabolism ◽  
Risk Model ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
Data Set ◽  
Molecular Features ◽  
Prognosis Group

Abstract Background: Dynamic balance of retinoic acid metabolism plays a major role in a variety of biological functions including cell proliferation and differentiation, while its dysregulation often leads to cancer progression and disordered immunity. Targeting retinoic acid signaling has shown effectivity in re-educates tumor microenvironment so that they could enhance the efficacy of immunotherapies and received better outcome. However, a comprehensive analysis of retinoic acid metabolism abnormality in sarcoma is still lacking, which limits the development and application of related targeted drugs.Methods: The RA metabolism related enzymes data set was collected from several database. Then we systematically analyzed the molecular features of 19 retinoic acid metabolism-related enzymes based on TCGA/TARGET/GSE datasets and revealed two subtypes with distinct metabolic status and prognostic value. And we further generated a 7 genes signature to predict retinoic acid metabolism index based on LASSO-penalized Cox regression model.Results: Gene set enrichment analysis indicated a set of immune and oncogenic pathways were enriched in poor-prognosis group. Connectivity Map screened 56 potential small molecules specific to different sub-groups. Survival analysis demonstrated significant prognostic difference between high- and low-risk groups among all datasets. Several immune cells including CD8+ T cells, Treg cells, Monocytes, and Macrophages showed different abundance between these groups, and immune checkpoint blockade therapy response prediction indicated potential immunotherapeutic efficiency of poor-prognosis group.Conclusions: Taken together, our study elaborated two different retinoic acid metabolism status of sarcoma, which revealed the metabolic heterogeneity of sarcoma. Robust and powerful metabolic index risk model could provide insightful suggestions to explore the molecular functions and mechanisms of retinoic acid metabolism.

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