scholarly journals Development of a Survival Model Based on Autophagy-Associated Genes for Predicting Prognosis of Gastric Cancer

2020 ◽  
Author(s):  
Wanli Yang ◽  
Lili Duan ◽  
Xinhui Zhao ◽  
Liaoran Niu ◽  
Yiding Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Prediction Model ◽  
Roc Curve ◽  
Survival Model ◽  
Differentially Expressed ◽  
Lasso Regression ◽  
Prognosis Prediction ◽  
Cellular Processes ◽  
Model Based

Abstract Background: Gastric cancer (GC) is one of lethal diseases worldwide. Autophagy-associated genes play a crucial role in the cellular processes of GC. Our study aimed to investigate and identify the prognostic potential of autophagy-associated genes signature in GC. Methods: RNA-seq and clinical information of GC and normal controls were downloaded from The Cancer Genome Atlas (TCGA) database. Then, the Wilcoxon signed-rank test was used to pick out the differentially expressed autophagy-associated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential roles and mechanisms of autophagy-associated genes in GC. Cox proportional hazard regression analysis and Lasso regression analysis were carried out to identify the overall survival (OS) related autophagy-associated genes, which were then collected to construct a predictive model. Kaplan-Meier method and receiver operating characteristic (ROC) curve were utilized to validate the accuracy of this model. Finally, a clinical nomogram was established by combining the clinical factors and autophagy-associated genes signature. Results: A total of 28 differentially expressed autophagy-associated genes were identified. GO and KEGG analyses revealed that several important cellular processes and signaling pathways were correlated with these genes. Through Cox regression and Lasso regression analyses, we identified 4 OS-related autophagy-associated genes (GRID2, ATG4D, GABARAPL2, and CXCR4) and constructed a prognosis prediction model. GC Patients with high-risk had a worse OS than those in low-risk group (5-year OS, 27.7% vs 38.3%; P=9.524e-07). The area under the ROC curve (AUC) of the prediction model was 0.67. The nomogram was demonstrated to perform better for predicting 3-year and 5-year survival possibility for GC patients with a concordance index (C-index) of 0.70 (95% CI: 0.65-0.72). The calibration curves also presented good concordance between nomogram-predicted survival and actual survival. Conclusions: We constructed and evaluated a survival model based on the autophagy-associated genes for GC patients, which may improve the prognosis prediction in GC.

Development and validation of a survival model based on autophagy-associated genes for predicting prognosis of hepatocellular carcinoma

2020 ◽  
Author(s):  
Wanli Yang ◽  
Liaoran Niu ◽  
Xinhui Zhao ◽  
Lili Duan ◽  
Yiding Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Survival Rate ◽  
Prediction Model ◽  
Risk Score ◽  
Cox Regression ◽  
Survival Model ◽  
Differentially Expressed ◽  
Lasso Regression ◽  
Prognostic Prediction

Abstract Background: Hepatocellular carcinoma (HCC) is one of the devastating tumors with increasing incidence. Autophagy-associated genes (ARGs) are widely participated in the cellular processes of HCC. This study proposed to identify the novel prognostic gene signature based on ARGs in HCC. Methods: We downloaded the RNA sequencing data and clinical information of HCC and normal tissues from The Cancer Genome Atlas (TCGA) database. The differentially expressed ARGs were screened by the Wilcoxon signed-rank test. Functional enrichment analyses were conducted to explore the biological implications and mechanisms of ARGs in HCC. Cox regression analysis and Lasso regression analysis were performed to screen the ARGs which related to overall survival (OS). The OS-related ARGs were then used to establish a prognostic prediction model. Kaplan-Meier curves and receiver operating characteristic (ROC) curves were both applied to evaluate the accuracy of the model. GSE14520 dataset was downloaded as the testing cohort to validate the prognostic risk model in TCGA. A nomogram based on the clinical features and risk signature was established to predict the 3-year and 5-year survival rate of HCC patients. Results: Totally 27 differentially expressed ARGs were screened in this study. Then, 3 OS-related ARGs (SQSTM1, HSPB8, and BIRC5) were identified via the Cox regression and Lasso regression analyses. Based on these 3 ARGs, a prognostic prediction model was constructed. HCC patients in high-risk group presented poorer prognosis than those with low risk score in TCGA cohort (3-year OS, 53.7% vs 70.2%; 5-year OS, 42.0 % vs 55.2%; P=4.478e-04) and in the testing group (3-year OS, 57.7% vs 73.5%; 5-year OS, 43.2% vs 63.0%; P=1.274e-03). The risk score curve showed a well feasibility in predicting the patients’ survival both in TCGA and GEO cohort with the area under the ROC curve (AUC) of 0.756 and 0.672, respectively. Besides, the calibration curves and C-index indicated that the clinical nomogram performs well to predict the 3-year and 5-year survival rate in HCC patients. Conclusions: The survival model based on the ARGs may be a promising tool to predict the prognosis in HCC patients.

scholarly journals The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chao Guo ◽  
Ya-yue Gao ◽  
Qian-qian Ju ◽  
Chun-xia Zhang ◽  
Ming Gong ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prediction Model ◽  
Hox Genes ◽  
Expression Profiles ◽  
Penalized Regression ◽  
Diagnostic Utility ◽  
Lasso Regression ◽  
Hub Genes ◽  
Npm1 Mutation ◽  
Genetic Abnormalities

Abstract Background The heterogenous cytogenetic and molecular variations were harbored by AML patients, some of which are related with AML pathogenesis and clinical outcomes. We aimed to uncover the intrinsic expression profiles correlating with prognostic genetic abnormalities by WGCNA. Methods We downloaded the clinical and expression dataset from BeatAML, TCGA and GEO database. Using R (version 4.0.2) and ‘WGCNA’ package, the co-expression modules correlating with the ELN2017 prognostic markers were identified (R2 ≥ 0.4, p < 0.01). ORA detected the enriched pathways for the key co-expression modules. The patients in TCGA cohort were randomly assigned into the training set (50%) and testing set (50%). The LASSO penalized regression analysis was employed to build the prediction model, fitting OS to the expression level of hub genes by ‘glmnet’ package. Then the testing and 2 independent validation sets (GSE12417 and GSE37642) were used to validate the diagnostic utility and accuracy of the model. Results A total of 37 gene co-expression modules and 973 hub genes were identified for the BeatAML cohort. We found that 3 modules were significantly correlated with genetic markers (the ‘lightyellow’ module for NPM1 mutation, the ‘saddlebrown’ module for RUNX1 mutation, the ‘lightgreen’ module for TP53 mutation). ORA revealed that the ‘lightyellow’ module was mainly enriched in DNA-binding transcription factor activity and activation of HOX genes. The ‘saddlebrown’ module was enriched in immune response process. And the ‘lightgreen’ module was predominantly enriched in mitosis cell cycle process. The LASSO- regression analysis identified 6 genes (NFKB2, NEK9, HOXA7, APRC5L, FAM30A and LOC105371592) with non-zero coefficients. The risk score generated from the 6-gene model, was associated with ELN2017 risk stratification, relapsed disease, and prior MDS history. The 5-year AUC for the model was 0.822 and 0.824 in the training and testing sets, respectively. Moreover, the diagnostic utility of the model was robust when it was employed in 2 validation sets (5-year AUC 0.743–0.79). Conclusions We established the co-expression network signature correlated with the ELN2017 recommended prognostic genetic abnormalities in AML. The 6-gene prediction model for AML survival was developed and validated by multiple datasets.

scholarly journals Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
High Efficiency ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Lasso Regression ◽  
Sequencing Data ◽  
Cox Regression Analysis

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

Multivariable Logistic Regression Equation to Predict Prostate Cancer

2021 ◽  
Author(s):  
Lu Ma ◽  
Dong Cheng ◽  
Qinghua Li ◽  
Jingbo Zhu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Prediction Model ◽  
Prostate Specific Antigen ◽  
Sensitivity And Specificity ◽  
Logistic Regression Analysis ◽  
Roc Curve ◽  
Specific Antigen ◽  
Clinical Feature

Abstract Objective: To explore the predictive value of white blood cell (WBC), monocyte (M), neutrophil-to-lymphocyte ratio (NLR), fibrinogen (FIB), free prostate-specific antigen (fPSA) and free prostate-specific antigen/prostate-specific antigen (f/tPSA) in prostate cancer (PCa).Materials and methods: Retrospective analysis of 200 cases of prostate biopsy and collection of patients' systemic inflammation indicators, biochemical indicators, PSA and fPSA. First, the dimensionality of the clinical feature parameters is reduced by the Lass0 algorithm. Then, the logistic regression prediction model was constructed using the reduced parameters. The cut-off value, sensitivity and specificity of PCa are predicted by the ROC curve analysis and calculation model. Finally, based on Logistic regression analysis, a Nomogram for predicting PCa is obtained.Results: The six clinical indicators of WBC, M, NLR, FIB, fPSA, and f/tPSA were obtained after dimensionality reduction by Lass0 algorithm to improve the accuracy of model prediction. According to the regression coefficient value of each influencing factor, a logistic regression prediction model of PCa was established: logit P=-0.018-0.010×WBC+2.759×M-0.095×NLR-0.160×FIB-0.306×fPSA-2.910×f/tPSA. The area under the ROC curve is 0.816. When the logit P intercept value is -0.784, the sensitivity and specificity are 72.5% and 77.8%, respectively.Conclusion: The establishment of a predictive model through Logistic regression analysis can provide more adequate indications for the diagnosis of PCa. When the logit P cut-off value of the model is greater than -0.784, the model will be predicted to be PCa.

scholarly journals Nomogram-Based Prediction of the Risk of Diabetic Retinopathy: A Retrospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ruohui Mo ◽  
Rong Shi ◽  
Yuhong Hu ◽  
Fan Hu
Keyword(s):  
Diabetic Retinopathy ◽  
Regression Analysis ◽  
Roc Curve ◽  
External Validation ◽  
Curve Analysis ◽  
Postprandial Blood Glucose ◽  
Lasso Regression ◽  
Prediction Ability ◽  
Decision Curve Analysis ◽  
Course Of Disease

Objectives. This study is aimed at developing a risk nomogram of diabetic retinopathy (DR) in a Chinese population with type 2 diabetes mellitus (T2DM). Methods. A questionnaire survey, biochemical indicator examination, and physical examination were performed on 4170 T2DM patients, and the collected data were used to evaluate the DR risk in T2DM patients. By operating R software, firstly, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection by running cyclic coordinate descent with 10 times K cross-validation. Secondly, multivariable logistic regression analysis was applied to build a predicting model introducing the predictors selected from the LASSO regression analysis. The nomogram was developed based on the selected variables visually. Thirdly, calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis were used to validate the model, and further assessment was running by external validation. Results. Seven predictors were selected by LASSO from 19 variables, including age, course of disease, postprandial blood glucose (PBG), glycosylated haemoglobin A1c (HbA1c), uric creatinine (UCR), urinary microalbumin (UMA), and systolic blood pressure (SBP). The model built by these 7 predictors displayed medium prediction ability with the area under the ROC curve of 0.700 in the training set and 0.715 in the validation set. The decision curve analysis curve showed that the nomogram could be applied clinically if the risk threshold is between 21% and 57% and 21%-51% in external validation. Conclusion. Introducing age, course of disease, PBG, HbA1c, UCR, UMA, and SBP, the risk nomogram is useful for prediction of DR risk in T2DM individuals.

scholarly journals A Risk Prediction Model Based on Lymph-Node Metastasis in Poorly Differentiated–Type Intramucosal Gastric Cancer

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0156207 ◽  
Author(s):  
Jeung Hui Pyo ◽  
Hyuk Lee ◽  
Byung-Hoon Min ◽  
Jun Haeng Lee ◽  
Min Gew Choi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Prediction Model ◽  
Risk Prediction ◽  
Risk Prediction Model ◽  
Node Metastasis ◽  
Model Based ◽  
Poorly Differentiated

scholarly journals Identification of Aging-Related Genes Associated With Clinical and Prognostic Features of Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Xingte Chen ◽  
Lei Wang ◽  
Liang Hong ◽  
Zhixiong Su ◽  
Xiaohong Zhong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
High Risk ◽  
Risk Score ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Survival Prediction ◽  
Lasso Regression ◽  
Prognostic Features

Background: Aging is a well-studied concept, but no studies have comprehensively analyzed the association between aging-related genes (AGs) and hepatocellular carcinoma (HCC) prognosis.Methods: Gene candidates were selected from differentially expressed genes and prognostic genes in The Cancer Genome Atlas (TCGA) database. A gene risk score for overall survival prediction was established using the least absolute shrinkage and selection operator (LASSO) regression analysis, and this was validated using data from the International Cancer Genome Consortium (ICGC) database. Functional analysis was conducted using gene ontology enrichment, Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis, and immune microenvironment and tumor stemness analyses.Results: Initially, 72 AGs from the TCGA database were screened as differentially expressed between normal and tumor tissues and as genes associated with HCC prognosis. Then, seven AGs (POLA1, CDK1, SOCS2, HDAC1, MAPT, RAE1, and EEF1E1) were identified using the LASSO regression analysis. The seven AGs were used to develop a risk score in the training set, and the risk was validated to have a significant prognostic value in the ICGC set (p &lt; 0.05). Patients with high risk scores had lower tumor differentiation, higher stage, and worse prognosis (all p &lt; 0.05). Multivariate Cox regression analyses also confirmed that the risk score was an independent prognostic factor for HCC in both the TCGA and ICGC sets (all p &lt; 0.05). Further analysis showed that a high risk score was correlated with the downregulation of metabolism and tumor immunity.Conclusion: The risk score predicts HCC prognosis and could thus be used as a biomarker not only for predicting HCC prognosis but also for deciding on treatment.

scholarly journals Integrated analysis of the functions and prognostic values of RNA-binding proteins in neuroblastoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260876
Author(s):  
Jun Yang ◽  
Jiaying Zhou ◽  
Cuili Li ◽  
Shaohua Wang
Keyword(s):  
Regression Analysis ◽  
Risk Score ◽  
Prognostic Model ◽  
Binding Proteins ◽  
Rna Binding ◽  
Risk Model ◽  
Cox Regression ◽  
Rna Binding Proteins ◽  
Differentially Expressed ◽  
Lasso Regression

Background Neuroblastoma (NB) is the most common solid tumor in children. NB treatment has made significant progress; however, given the high degree of heterogeneity, basic research findings and their clinical application to NB still face challenges. Herein, we identify novel prognostic models for NB. Methods We obtained RNA expression data of NB and normal nervous tissue from TARGET and GTEx databases and determined the differential expression patterns of RNA binding protein (RBP) genes between normal and cancerous tissues. Lasso regression and Cox regression analyses identified the five most important differentially expressed genes and were used to construct a new prognostic model. The function and prognostic value of these RBPs were systematically studied and the predictive accuracy verified in an independent dataset. Results In total, 348 differentially expressed RBPs were identified. Of these, 166 were up-regulated and 182 down-regulated RBPs. Two hubs RBPs (CPEB3 and CTU1) were identified as prognostic-related genes and were chosen to build the prognostic risk score models. Multivariate Cox analysis was performed on genes from univariate Cox regression and Lasso regression analysis using proportional hazards regression model. A five gene prognostic model: Risk score = (-0.60901*expCPEB3)+(0.851637*expCTU1) was built. Based on this model, the overall survival of patients in the high-risk subgroup was lower (P = 2.152e-04). The area under the curve (AUC) of the receiver-operator characteristic curve of the prognostic model was 0.720 in the TARGET cohort. There were significant differences in the survival rate of patients in the high and low-risk subgroups in the validation data set GSE85047 (P = 0.1237e-08), with the AUC 0.730. The risk model was also regarded as an independent predictor of prognosis (HR = 1.535, 95% CI = 1.368–1.722, P = 2.69E-13). Conclusions This study identified a potential risk model for prognosis in NB using Cox regression analysis. RNA binding proteins (CPEB3 and CTU1) can be used as molecular markers of NB.

scholarly journals The Prediction Model of Risk Factors for COVID-19 Developing into Severe Illness Based on 1046 Patients with COVID-19

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhichuang Lian ◽  
Yafang Li ◽  
Wenyi Wang ◽  
Wei Ding ◽  
Zongxin Niu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Prediction Model ◽  
Logistic Regression Analysis ◽  
Roc Curve ◽  
Curve Analysis ◽  
Severe Illness ◽  
Roc Curve Analysis ◽  
Underlying Diseases

This study analyzed the risk factors for patients with COVID-19 developing severe illnesses and explored the value of applying the logistic model combined with ROC curve analysis to predict the risk of severe illnesses at COVID-19 patients’ admissions. The clinical data of 1046 COVID-19 patients admitted to a designated hospital in a certain city from July to September 2020 were retrospectively analyzed, the clinical characteristics of the patients were collected, and a multivariate unconditional logistic regression analysis was used to determine the risk factors for severe illnesses in COVID-19 patients during hospitalization. Based on the analysis results, a prediction model for severe conditions and the ROC curve were constructed, and the predictive value of the model was assessed. Logistic regression analysis showed that age (OR = 3.257, 95% CI 10.466–18.584), complications with chronic obstructive pulmonary disease (OR = 7.337, 95% CI 0.227–87.021), cough (OR = 5517, 95% CI 0.258–65.024), and venous thrombosis (OR = 7322, 95% CI 0.278–95.020) were risk factors for COVID-19 patients developing severe conditions during hospitalization. When complications were not taken into consideration, COVID-19 patients’ ages, number of diseases, and underlying diseases were risk factors influencing the development of severe illnesses. The ROC curve analysis results showed that the AUC that predicted the severity of COVID-19 patients at admission was 0.943, the optimal threshold was −3.24, and the specificity was 0.824, while the sensitivity was 0.827. The changes in the condition of severe COVID-19 patients are related to many factors such as age, clinical symptoms, and underlying diseases. This study has a certain value in predicting COVID-19 patients that develop from mild to severe conditions, and this prediction model is a useful tool in the quick prediction of the changes in patients’ conditions and providing early intervention for those with risk factors.

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