Clinicopathological signature and prognostic value of RNA:m5C methyltransferases in gliomas

2020 ◽  
Author(s):  
Peng Wang ◽  
Kai Huang ◽  
Miaojing Wu ◽  
Qing Hu ◽  
Chuming Tao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Score ◽  
Prognostic Value ◽  
Cox Regression ◽  
Roc Curves ◽  
Clinicopathological Features ◽  
Gene Set Enrichment Analysis ◽  
Consensus Clustering ◽  
Score Model ◽  
Genome Atlas

Abstract Background: Glioma is the most common primary intracranial tumor, accounting for the vast majority of intracranial malignant tumors. Aberrant expression of RNA:5-methylcytosine(m5C) methyltransferases has recently been the focus of research relating to the occurrence and progression of tumors. However, the prognostic value of RNA:m5C methyltransferases in glioma remains unclear. This study investigated RNA: m5C methyltransferase expression and defined its clinicopathological signature and prognostic value in gliomas. Methods: We systematically studied the RNA-sequence data of RNA:m5C methyltransferases underlying gliomas in the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets and identified different subtypes using Consensus clustering analysis. Gene Ontology (GO) and Gene Set Enrichment analysis (GSEA) was used to annotate the function of these genes. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm analyses were performed to construct the risk score model. Kaplan-Meier method and Receiver operating characteristic (ROC) curves were used to assess the overall survival of glioma patients. Additionally, Cox proportional regression model analysis was developed to address the connections between the risk scores and clinical factors. Results: Consensus clustering of RNA:m5C methyltransferases identified three clusters of gliomas with different prognostic and clinicopathological features. Meanwhile, Functional annotations demonstrated that RNA:m5C methyltransferases were significantly associated with the malignant progression of gliomas. Thereafter, five RNA:m5C methyltransferase genes were screened to construct a risk score model which can be used to predict not only overall survival but also clinicopathological features in gliomas. ROC curves revealed the significant prognostic ability of this signature. In addition, Multivariate Cox regression analyses indicated that the risk score was an independent prognostic factor for glioma outcome. Conclusion: We demonstrated the role of RNA:m5C methyltransferases in the initiation and progression of glioma. We have expanded on the understanding of the molecular mechanism involved, and provided a unique approach to predictive biomarkers and targeted therapy.

scholarly journals A Five-lncRNAs Signature-Derived Risk Score Based on TCGA and CGGA for Glioblastoma: Potential Prospects for Treatment Evaluation and Prognostic Prediction

2020 ◽  
Vol 10 ◽  
Author(s):  
Xuegang Niu ◽  
Jiangnan Sun ◽  
Lingyin Meng ◽  
Tao Fang ◽  
Tongshuo Zhang ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Therapeutic Efficacy ◽  
Cox Regression ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Normal Brain ◽  
Score Model ◽  
Genome Atlas

Accumulating studies have confirmed the crucial role of long non-coding RNAs (ncRNAs) as favorable biomarkers for cancer diagnosis, therapy, and prognosis prediction. In our recent study, we established a robust model which is based on multi-gene signature to predict the therapeutic efficacy and prognosis in glioblastoma (GBM), based on Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. lncRNA-seq data of GBM from TCGA and CGGA datasets were used to identify differentially expressed genes (DEGs) compared to normal brain tissues. The DEGs were then used for survival analysis by univariate and multivariate COX regression. Then we established a risk score model, depending on the gene signature of multiple survival-associated DEGs. Subsequently, Kaplan-Meier analysis was used for estimating the prognostic and predictive role of the model. Gene set enrichment analysis (GSEA) was applied to investigate the potential pathways associated to high-risk score by the R package “cluster profile” and Wiki-pathway. And five survival associated lncRNAs of GBM were identified: LNC01545, WDR11-AS1, NDUFA6-DT, FRY-AS1, TBX5-AS1. Then the risk score model was established and shows a desirable function for predicting overall survival (OS) in the GBM patients, which means the high-risk score significantly correlated with lower OS both in TCGA and CGGA cohort. GSEA showed that the high-risk score was enriched with PI3K-Akt, VEGFA-VEGFR2, TGF-beta, Notch, T-Cell pathways. Collectively, the five-lncRNAs signature-derived risk score presented satisfactory efficacies in predicting the therapeutic efficacy and prognosis in GBM and will be significant for guiding therapeutic strategies and research direction for GBM.

Immune-related gene based prognostic signature for the risk stratification analysis of breast cancer

2021 ◽  
Vol 16 ◽  
Author(s):  
Dongqing Su ◽  
Qianzi Lu ◽  
Yi Pan ◽  
Yao Yu ◽  
Shiyuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis ◽  
Score Model

Background: Breast cancer has plagued women for many years and caused many deaths around the world. Method: In this study, based on the weighted correlation network analysis, univariate Cox regression analysis and least absolute shrinkage and selection operator, 12 immune-related genes were selected to construct the risk score for breast cancer patients. The multivariable Cox regression analysis, gene set enrichment analysis and nomogram were also conducted in this study. Results: Good results were obtained in the survival analysis, enrichment analysis, multivariable Cox regression analysis and immune-related feature analysis. When the risk score model was applied in 22 breast cancer cohorts, the univariate Cox regression analysis demonstrated that the risk score model was significantly associated with overall survival in most of the breast cancer cohorts. Conclusion: Based on these results, we could conclude that the proposed risk score model may be a promising method, and may improve the treatment stratification of breast cancer patients in the future work.

scholarly journals Development of an Immune Infiltration-Related Eight-Gene Prognostic Signature in Colorectal Cancer Microenvironment

2020 ◽  
Vol 2020 ◽  
pp. 1-43
Author(s):  
Beilei Wu ◽  
Lijun Tao ◽  
Daqing Yang ◽  
Wei Li ◽  
Hongbo Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Immune Cells ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Roc Curves ◽  
Functional Enrichment ◽  
Cox Regression Analysis ◽  
Immune Genes ◽  
Score Model

Objective. Stromal cells and immune cells have important clinical significance in the microenvironment of colorectal cancer (CRC). This study is aimed at developing a CRC gene signature on the basis of stromal and immune scores. Methods. A cohort of CRC patients (n=433) were adopted from The Cancer Genome Atlas (TCGA) database. Stromal/immune scores were calculated by the ESTIMATE algorithm. Correlation between prognosis/clinical characteristics and stromal/immune scores was assessed. Differentially expressed stromal and immune genes were identified. Their potential functions were annotated by functional enrichment analysis. Cox regression analysis was used to develop an eight-gene risk score model. Its predictive efficacies for 3 years, 5 years, overall survival (OS), and progression-free survival interval (PFI) were evaluated using time-dependent receiver operating characteristic (ROC) curves. The correlation between the risk score and the infiltering levels of six immune cells was analyzed using TIMER. The risk score was validated using an independent dataset. Results. Immune score was in a significant association with prognosis and clinical characteristics of CRC. 736 upregulated and two downregulated stromal and immune genes were identified, which were mainly enriched into immune-related biological processes and pathways. An-eight gene prognostic risk score model was conducted, consisting of CCL22, CD36, CPA3, CPT1C, KCNE4, NFATC1, RASGRP2, and SLC2A3. High risk score indicated a poor prognosis of patients. The area under the ROC curves (AUC) s of the model for 3 years, 5 years, OS, and PFI were 0.71, 0.70, 0.73, and 0.66, respectively. Thus, the model possessed well performance for prediction of patients’ prognosis, which was confirmed by an external dataset. Moreover, the risk score was significantly correlated with immune cell infiltration. Conclusion. Our study conducted an immune-related prognostic risk score model, which could provide novel targets for immunotherapy of CRC.

scholarly journals The Landscape of Glycosyltransferase Gene Signature for Overall Survival Prediction in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Qiang Cai ◽  
Shizhe Yu ◽  
Jian Zhao ◽  
Duo Ma ◽  
Long Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Risk Score ◽  
Prognostic Value ◽  
Cox Regression ◽  
Risk Groups ◽  
Gene Signature ◽  
Low Risk ◽  
Regression Analyses ◽  
Risk Patients

Abstract Background: Hepatocellular carcinoma (HCC) is heterogeneous disease occurring in the background of chronic liver diseases. The role of glycosyltransferase (GT) genes have recently been the focus of research associating with the development of tumors. However, the prognostic value of GT genes in HCC remains not elucidated. This study aimed to demonstrate the GT genes related to the prognosis of HCC through bioinformatics analysis.Methods: The GT genes signatures were identified from the training set of The Cancer Genome Atlas (TCGA) dataset using univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Then, we analyzed the prognostic value of GT genes signatures related to the overall survival (OS) of HCC patients. A prognostic model was constructed, and the risk score of each patient was calculated as formula, which divided HCC patients into high- and low-risk groups. Kaplan-Meier (K-M) and Receiver operating characteristic (ROC) curves were used to assess the OS of HCC patients. The prognostic value of GT genes signatures was further investigated in the validation set of TCGA database. Univariate and multivariate Cox regression analyses were performed to demonstrate the independent factors on OS. Finally, we utilized the gene set enrichment analysis (GSEA) to annotate the function of these genes between the two risk categories. Results: In this study, we identified and validated 4 GT genes as the prognostic signatures. The K-M analysis showed that the survival rate of the high-risk patients was significantly lower than that of the low-risk patients. The risk score calculated with 4 gene signatures could predict OS for 3-, 5-, and 7-year in patients with HCC, revealing the prognostic ability of these gene signature. In addition, Multivariate Cox regression analyses indicated that the risk score was an independent prognostic factor for HCC. Functional analysis further revealed that immune-related pathways were enriched, and immune status in HCC were different between the two risk groups.Conclusion: In conclusion, a novel GT genes signature can be used for prognostic prediction in HCC. Thus, targeting GT genes may be a therapeutic alternative for HCC.

scholarly journals Combination of Immune-Related Genomic Alterations Reveals Immune Characterization and Prediction of Different Prognostic Risks in Ovarian Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xibo Zhao ◽  
Shanshan Cong ◽  
Qiuyan Guo ◽  
Yan Cheng ◽  
Tian Liang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Risk Score ◽  
Immune Cell ◽  
Cox Regression ◽  
Case Fatality ◽  
The Cancer Genome Atlas ◽  
Genomic Alterations ◽  
Predictive Values ◽  
Score Model

With the highest case-fatality rate among women, the molecular pathological alterations of ovarian cancer (OV) are complex, depending on the diversity of genomic alterations. Increasing evidence supports that immune infiltration in tumors is associated with prognosis. Therefore, we aim to assess infiltration in OV using multiple methods to capture genomic signatures regulating immune events to identify reliable predictions of different outcomes. A dataset of 309 ovarian serous cystadenocarcinoma patients with overall survival >90 days from The Cancer Genome Atlas (TCGA) was analyzed. Multiple estimations and clustering methods identified and verified two immune clusters with component differences. Functional analyses pointed out immune-related alterations underlying internal genomic variables potentially. After extracting immune genes from a public database, the LASSO Cox regression model with 10-fold cross-validation was used for selecting genes associated with overall survival rate significantly, and a risk score model was then constructed. Kaplan–Meier survival and Cox regression analyses among cohorts were performed systematically to evaluate prognostic efficiency among the risk score model and other clinical pathological parameters, establishing a predictive ability independently. Furthermore, this risk score model was compared among identified signatures in previous studies and applied to two external cohorts, showing better prediction performance and generalization ability, and also validated as robust in association with immune cell infiltration in bulk tissues. Besides, a transcription factor regulation network suggested upper regulatory mechanisms in OV. Our immune risk score model may provide gyneco-oncologists with predictive values for the prognosis and treatment management of patients with OV.

scholarly journals Identification Sixteen Metabolic Genes as Potential Biomarkers for Colon Adenocarcinoma 

2020 ◽  
Author(s):  
Binbin Cui ◽  
Fuqiang Zhao ◽  
Yanlong Liu ◽  
Xinyue Gu ◽  
Bomiao Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Risk Score ◽  
Cox Regression ◽  
Colon Adenocarcinoma ◽  
Curve Analysis ◽  
Gene Set Enrichment Analysis ◽  
Risk Scores ◽  
Metabolic Genes ◽  
Cox Analysis

Abstract Purpose Colon adenocarcinoma (COAD) is the most common primary malignant tumor of the digestive tract. It is still important to find important markers that affect the prognosis of COAD. This research aims to identify some key prognosis-related metabolic genes (PRMG) and establish a clinical prognosis model for COAD patients. Method We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to obtain gene expression profiles of COAD, and then identified differentially expressed prognostic-related metabolic genes through R language and Perl software, Through univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis to obtain target genes, established metabolic genes prognostic models and risk scores. Through COX regression analysis, independent risk factors affecting the prognosis of COAD were analyzed, and Receiver Operating Characteristic (ROC) curve analysis of independent prognostic factors was performed and a nomogram for predicting overall survival was constructed. Perform the consistency index (C-index) test and decision curve analysis (DCA) on the nomogram, and use Gene Set Enrichment Analysis (GSEA) to identify the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of model genes. Result We selected PRMG based on the expression of metabolic genes, and used LASSO Cox regression to construct 16 metabolic gene (SEPHS1, P4HA1, ENPP2, PTGDS, GPX3, CP, ASPA, POLR3A, PKM, POLR2D , XDH, EPHX2, ADH1B, HMGCL, GPD1L and MAOA) models. The risk score generated from our model can well predict the survival prognosis of COAD. A nomogram based on the clinicopathological characteristics and risk scores of COAD can personally predict the overall survival rate of COAD patients. Conclusion We comprehensively identified metabolic genes related to the prognosis of COAD. The risk score based on the expression of 16 metabolic genes can effectively predict the prognosis of patients with COAD.

scholarly journals Development and Verification of Glutamatergic Synapse-Associated Prognosis Signature for Lower-Grade Gliomas

2021 ◽  
Vol 14 ◽  
Author(s):  
Liguo Ye ◽  
Yang Xu ◽  
Ping Hu ◽  
Long Wang ◽  
Ji’an Yang ◽  
...  
Keyword(s):  
Risk Score ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
Normal Brain ◽  
Lower Grade ◽  
Glutamatergic Synapse ◽  
Hub Genes ◽  
Gene Set ◽  
Genome Atlas

Background: Lower-grade glioma (LGG) is the most common histology identified in gliomas, a heterogeneous tumor that may develop into high-grade malignant glioma that seriously shortens patient survival time. Recent studies reported that glutamatergic synapses might play an essential role in the progress of gliomas. However, the role of glutamatergic synapse-related biomarkers in LGG has not been systemically researched yet.Methods: The mRNA expression data of glioma and normal brain tissue were obtained from The Cancer Genome Atlas database and Genotype-Tissue Expression, respectively, and the Chinese Glioma Genome Atlas database was used as a validation set. Difference analysis was performed to evaluate the expression pattern of glutamatergic synapse-related genes (GSRGs) in LGG. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct the glutamatergic synapse-related risk signature (GSRS), and the risk score of each LGG sample was calculated based on the coefficients and expression value of selected GSRGs. Univariate and multivariate Cox regression analyses were used to investigate the prognostic value of risk score. Immunity profile and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the association between risk score and the characters of tumor microenvironment in LGG. Gene set variation analysis (GSVA) was performed to investigate the potential pathways related to GSRS. The HPA database and real-time PCR were used to identify the expression of hub genes identified in GSRS.Results: A total of 22 genes of 39 GSRGs were found differentially expressed among normal and LGG samples. Through the LASSO algorithm, 14-genes GSRS constructed were associated with the prognosis and clinicopathological features of patients with LGG. Furthermore, the risk score level was significantly positively correlated with the infiltrating level of immunosuppressive cells, including M2 macrophages and regulatory T cells. GSVA identified a series of cancer-related pathways related to GSRS, such as P13K-AKT and P53 pathways. Moreover, ATAD1, NLGN2, OXTR, and TNR, hub genes identified in GSRS, were considered as potential prognostic biomarkers in LGG.Conclusion: A 14-genes GSRS was constructed and verified in this study. We provided a novel insight into the role of GSRS in LGG through a series of bioinformatics methods.

scholarly journals Integrated analysis of autophagy-related genes(ATGs) reveals the prognostic value of oral squamous cell carcinoma

2020 ◽  
Author(s):  
Guangzhao Huang ◽  
Zhi-yun Li ◽  
Yu Rao ◽  
Xiao-zhi Lv
Keyword(s):  
Survival Analysis ◽  
Signaling Pathway ◽  
Risk Score ◽  
Prognostic Value ◽  
Risk Model ◽  
Cox Regression ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Score Model

Abstract Background: Increasing evidence demonstrated that autophagy paly a crucial role in initiation and progression of OSCC. The aim of this study was to explore the prognostic value of autophagy-related genes(ATGs) in patients with OSCC. RNA-seq and clinical data were downloaded from TCGA database following extrating ATGs expression profiles. Then, differentially expressed analysis was performed in R software EdgeR package, and the potential biological function of differentially expressed ATGs were explored by GO and KEGG enrichment analysis. Furthermore, a risk score model based on ATGs was constructed to predict the overall survival. Moreover, univariate, multivariate cox regression and survival analysis were used to select autophagy related biomarkers which were identified by RT-qPCR in OSCC cell lines, OSCC tissues and matched normal mucosal tissues. Results: Total of 232 ATGs were extrated and 37 genes were differentially expressed in OSCC. GO and KEGG analysis indicated that these differentially expressed genes were mainly located in autophagosome membrane, and associated with apoptosis, platinum drug resistance, ErbB signaling pathway and TNF signaling pathway. Furthermore, a risk score model including 9 variables was constructed and subsequently identified with univariate, multivariate cox regression, survival analysis and Receiver Operating Characteristic curve(ROC). Moreover, ATG12 and BID were identified as potential autophagy related biomakers. Conclusion: This study successfully constructed a risk model to predict the prognosis of patients with OSCC, and the risk score may be as a independent prognostic biomarker in OSCC. ATG12 and BID were identified as potential biomarkers in tumor diagnosis and treatment of OSCC.

scholarly journals The Prognostic Value of an autophagy-related lncRNA Signature in Esophageal Cancer

2021 ◽  
Author(s):  
Zhiyong Zhang ◽  
Weiyun Bi ◽  
Yan Zhao ◽  
Mudan Ren ◽  
Yarui Li ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Risk Score ◽  
Prognostic Value ◽  
Roc Curves ◽  
The Cancer Genome Atlas ◽  
Screening Criteria ◽  
Rna Transcripts ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Score Model

Abstract Esophageal cancer is a clinically challenging disease, seriously affecting the quality of life and prognosis of patients. Autophagy is a basic intracellular event that can maintain cell homeostasis by degrading damaged or degenerate proteins and organelles. Long noncoding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides that participate in fundamental biological processes and tumor progression. However, whether autophagy-related lncRNAs can be used to predict the survival of patients with esophageal cancer still needs in-depth research. The Human Autophagy Database19 (HADb) and The Cancer Genome Atlas (TCGA) database were used to identify autophagy-related lncRNAs. Univariate and multivariate COX analyses were performed to establish a prognostic risk score model. Kaplan–Meier curves and ROC curves were carried out to evaluate the prognostic value of the autophagy-related lncRNAs signature. 1757 autophagy-related lncRNAs in esophageal cancer were identified based on specific screening criteria and four key lncRNAs (ZFAS1, AC092687.3, AC083799.1, AL080317.1) were selected to construct a novel prognostic model. Particularly, the risk score for each patient could be calculated based on the expression levels of these four lncRNAs, and a high risk score was positively associated with shorter survival time and poor prognosis of esophageal cancer patients. The autophagy-related lncRNAs signature constructed in this study can be used as a novel risk score model to predict the survival and prognosis of patients with esophageal cancer.

scholarly journals Angiogenesis-Related Gene Expression Signatures Predicting Prognosis in Gastric Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3685
Author(s):  
Haoyu Ren ◽  
Jiang Zhu ◽  
Haochen Yu ◽  
Alexandr Bazhin ◽  
Christoph Westphalen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Risk Score ◽  
Cox Regression ◽  
Clinical Stage ◽  
External Validation ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Related Gene ◽  
Angiogenesis Related Gene

Increasing evidence indicates that angiogenesis is crucial in the development and progression of gastric cancer (GC). This study aimed to develop a prognostic relevant angiogenesis-related gene (ARG) signature and a nomogram. The expression profile of the 36 ARGs and clinical information of 372 GC patients were extracted from The Cancer Genome Atlas (TCGA). Consensus clustering was applied to divide patients into clusters 1 and 2. Least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to identify the survival related ARGs and establish prognostic gene signatures, respectively. The Asian Cancer Research Group (ACRG) (n = 300) was used for external validation. Risk score of ARG signatures was calculated, and a prognostic nomogram was developed. Gene set enrichment analysis of the ARG model risk score was performed. Cluster 2 patients had more advanced clinical stage and shorter survival rates. ARG signatures carried prognostic relevance in both cohorts. Moreover, ARG-risk score was proved as an independent prognostic factor. The predictive value of the nomogram incorporating the risk score and clinicopathological features was superior to tumor, lymph node, metastasis (TNM) staging. The high-risk score group was associated with several cancer and metastasis-related pathways. The present study suggests that ARG-based nomogram could serve as effective prognostic biomarkers and allow a more precise risk stratification.

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