scholarly journals Establishment of an Autophagy-Related Clinical Prognosis Model for Predicting the Overall Survival of Osteosarcoma

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Jianyi Li ◽  
Xiaojie Tang ◽  
Yukun Du ◽  
Jun Dong ◽  
Zheng Zhao ◽  
...  

Purpose. Osteosarcoma is the most common primary and highly invasive bone tumor in children and adolescents. The purpose of this study is to construct a multi-gene expression feature related to autophagy, which can be used to predict the prognosis of patients with osteosarcoma. Materials and methods. The clinical and gene expression data of patients with osteosarcoma were obtained from the target database. Enrichment analysis of autophagy-related genes related to overall survival (OS-related ARGs) screened by univariate Cox regression was used to determine OS-related ARGs function and signal pathway. In addition, the selected OS-related ARGs were incorporated into multivariate Cox regression to construct prognostic signature for the overall survival (OS) of osteosarcoma. Use the dataset obtained from the GEO database to verify the signature. Besides, gene set enrichment analysis (GSEA) were applied to further elucidate the molecular mechanisms. Finally, the nomogram is established by combining the risk signature with the clinical characteristics. Results. Our study eventually included 85 patients. Survival analysis showed that patients with low riskScore had better OS. In addition, 16 genes were included in OS-related ARGs. We also generate a prognosis signature based on two OS-related ARGs. The signature can significantly divide patients into low-risk groups and high-risk groups, and has been verified in the data set of GEO. Subsequently, the riskScore, primary tumor site and metastasis status were identified as independent prognostic factors for OS and a nomogram were generated. The C-index of nomogram is 0.789 (95% CI: 0.703~0.875), ROC curve and calibration chart shows that nomogram has a good consistency between prediction and observation of patients. Conclusions. ARGs was related to the prognosis of osteosarcoma and can be used as a biomarker of prognosis in patients with osteosarcoma. Nomogram can be used to predict OS of patients and improve treatment strategies.

2021 ◽  
Author(s):  
Qian He ◽  
Yi Cao ◽  
Yue Zhao ◽  
Yi Shen ◽  
Xiong Xu ◽  
...  

Abstract Idiopathic pulmonary fibrosis (IPF), caused by a strange reason and characterized by a bad clinical prognosis, is an advanced, long-time, and irreversible interstitial lung disease (ILD). In recent years, it has been confirmed that a pyroptosis is a phlogistic form of programmed cellular demise. At the same time, the expression of the pyroptosis-participant gene (PPG) in IPF and their pertinence behind prognosis remains indistinct. In this research, we identified 17 pyroptosis regulators that were distinguishingly expressed entre IPF and controls. The ground on these distinguishingly expressed genes (DEGs), entire IPF conditions could be uncoupled into two subtypes. The prognostic significance of respective PPG for surviving was assessed to find a polygenes signature doing with a Gene Expression Omnibus (GEO) pack (GSE28042). Via putting into use the least absolute shrinkage and selection operator (LASSO) Cox regression approach, a 6-gene signature was structured and ranged entire IPF sicks in GSE28042 into a shallow-threat or high-threat group. IPF sicks in the shallow-threat group revealed meaningfully upper survival chances than those in the high-threat group (pvalue < 0.001). Exploiting the mid threat-score from GSE28042, IPF sicks from another GEO cohort(GSE70866-GPL17077) were separated into two threat subgroups, and the shallow-threat set had augmented overall survival (OS) time ( P = 0.0018). United the clinical characteristics, the threat-score was a sole element for forecasting the overall survival of IPF sicks. Function enrichment analyses bespoke that modification of morphology or physiology of other organisms, killing of cellular of other organisms, and disruption of cellular of other organisms biological processes were increased in the high-threat group. GSEA(Gene Set Enrichment Analysis) showed that cancer- and autoimmune disease-participant “KEGG” gene sets were highly enriched in the high−threat phenotype. In general, PPGs play a crucial role in IPF and can be done to forecast the prognosis of IPFs, and our consequences suggest that the high-threat group of IPF may be linked with the response of other organisms and autoimmunity as well.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11273
Author(s):  
Lei Yang ◽  
Weilong Yin ◽  
Xuechen Liu ◽  
Fangcun Li ◽  
Li Ma ◽  
...  

Background Hepatocellular carcinoma (HCC) is considered to be a malignant tumor with a high incidence and a high mortality. Accurate prognostic models are urgently needed. The present study was aimed at screening the critical genes for prognosis of HCC. Methods The GSE25097, GSE14520, GSE36376 and GSE76427 datasets were obtained from Gene Expression Omnibus (GEO). We used GEO2R to screen differentially expressed genes (DEGs). A protein-protein interaction network of the DEGs was constructed by Cytoscape in order to find hub genes by module analysis. The Metascape was performed to discover biological functions and pathway enrichment of DEGs. MCODE components were calculated to construct a module complex of DEGs. Then, gene set enrichment analysis (GSEA) was used for gene enrichment analysis. ONCOMINE was employed to assess the mRNA expression levels of key genes in HCC, and the survival analysis was conducted using the array from The Cancer Genome Atlas (TCGA) of HCC. Then, the LASSO Cox regression model was performed to establish and identify the prognostic gene signature. We validated the prognostic value of the gene signature in the TCGA cohort. Results We screened out 10 hub genes which were all up-regulated in HCC tissue. They mainly enrich in mitotic cell cycle process. The GSEA results showed that these data sets had good enrichment score and significance in the cell cycle pathway. Each candidate gene may be an indicator of prognostic factors in the development of HCC. However, hub genes expression was weekly associated with overall survival in HCC patients. LASSO Cox regression analysis validated a five-gene signature (including CDC20, CCNB2, NCAPG, ASPM and NUSAP1). These results suggest that five-gene signature model may provide clues for clinical prognostic biomarker of HCC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chunxia Zhao ◽  
Yulu Wang ◽  
Famei Tu ◽  
Shuai Zhao ◽  
Xiaoying Ye ◽  
...  

BackgroundSome studies have proven that autophagy and lncRNA play important roles in AML. Several autophagy related lncRNA signatures have been shown to affect the survival of patients in some other cancers. However, the role of autophagy related lncRNA in AML has not been explored yet. Hence, this study aims to find an autophagy related lncRNA signature that can affect survival for AML patients.MethodA Pearson correlation analysis, a Kaplan–Meier survival curve, a univariate cox regression, and a multivariate cox regression were performed to establish an autophagy related lncRNA signature. A univariate cox regression, a multivariate cox regression, a Kaplan–Meier survival curve, and a ROC curve were applied to confirm if the signature is an independent prognosis for AML patients. The relationship between the signature and the clinical features was explored by using a T test. Gene Set Enrichment Analysis (GSEA) was used to investigate the potential tumor related pathways.ResultsA four-autophagy related lncRNA (MIR133A1HG, AL359715.1, MIRLET7BHG, and AL356752.1) signature was established. The high risk score based on signature was related to the short survival time of AML patients. The signature was an independent factor for the prognosis for AML patients (HR = 1.684, 95% CI = 1.324–2.142, P &lt; 0.001). The signature was correlated with age, leukocyte numbers, and FAB (M3 or non-M3). The P53, IL6/JAK/STAT3, TNF-α, INF-γ, and IL2/STAT5 pathways might contribute to the differences between the risk groups based on signature in AML.ConclusionThe four autophagy related lncRNAs and their signature might be novel biomarkers for predicting the survival of AML patients. Some biological pathways might be the potential mechanisms of the signature for the survival of AML patients.


Author(s):  
Bo Xiao ◽  
Liyan Liu ◽  
Zhuoyuan Chen ◽  
Aoyu Li ◽  
Pingxiao Wang ◽  
...  

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial–mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database (N = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zhen Tan ◽  
Yubin Lei ◽  
Bo Zhang ◽  
Si Shi ◽  
Jiang Liu ◽  
...  

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most invasive solid malignancies. Immunotherapy and targeted therapy confirmed an existing certain curative effect in treating PDAC. The aim of this study was to develop an immune-related molecular marker to enhance the ability to predict Stages III and IV PDAC patients.MethodIn this study, weighted gene co-expression network (WGCNA) analysis and a deconvolution algorithm (CIBERSORT) that evaluated the cellular constituent of immune cells were used to evaluate PDAC expression data from the GEO (Gene Expression Omnibus) datasets, and identify modules related to CD4+ T cells. LASSO Cox regression analysis and Kaplan–Meier curve were applied to select and build prognostic multi-gene signature in TCGA Stages III and IV PDAC patients (N = 126). This was followed by independent Stages III and IV validation of the gene signature in the International Cancer Genome Consortium (ICGC, N = 62) and the Fudan University Shanghai Cancer Center (FUSCC, N = 42) cohort. Inherited germline mutations and tumor immunity exploration were applied to elucidate the molecular mechanisms in PDAC. Univariate and Multivariate Cox regression analyses were applied to verify the independent prognostic factors. Finally, a prognostic nomogram was created according to the TCGA-PDAC dataset.ResultsA four-gene signature comprising NAPSB, ZNF831, CXCL9 and PYHIN1 was established to predict overall survival of PDAC. This signature also robustly predicted survival in two independent validation cohorts. The four-gene signature could divide patients into high and low-risk groups with disparity overall survival verified by a Log-rank test. Expression of four genes positively correlated with immunosuppression activity (PD-L1 and PD1). Immune-related genes nomogram and corresponding calibration curves showed significant performance for predicting 3-year survival in TCGA-PDAC dataset.ConclusionWe constructed a novel four-gene signature to predict the prognosis of Stages III and IV PDAC patients by applying WGCNA and CIBERSORT algorithm scoring to transcriptome data different from traditional methods of filtrating for differential genes in cancer and healthy tissues. The findings may provide reference to predict survival and was beneficial to individualized management for advanced PDAC patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Xinheng Liu ◽  
Yongxian Rong ◽  
Donglin Huang ◽  
Zhijie Liang ◽  
Xiaolin Yi ◽  
...  

Severe burns are acute wounds caused by local heat exposure, resulting in life-threatening systemic effects and poor survival. However, the specific molecular mechanisms remain unclear. First, we downloaded gene expression data related to severe burns from the GEO database (GSE19743, GSE37069, and GSE77791). Then, a gene expression analysis was performed to identify differentially expressed genes (DEGs) and construct protein-protein interaction (PPI) network. The molecular mechanism was identified by enrichment analysis and Gene Set Enrichment Analysis. In addition, STEM software was used to screen for genes persistently expressed during response to severe burns, and receiver operating characteristic (ROC) curve was used to identify key DEGs. A total of 2631 upregulated and 3451 downregulated DEGs were identified. PPI network analysis clustered these DEGs into 13 modules. Importantly, module genes mostly related with immune responses and metabolism. In addition, we identified genes persistently altered during the response to severe burns corresponding to survival and death status. Among the genes with high area under the ROC curve in the PPI network gene, CCL5 and LCK were identified as key DEGs, which may affect the prognosis of burn patients. Gene set variation analysis showed that the immune response was inhibited and several types of immune cells were decreased, while the metabolic response was enhanced. The results showed that persistent gene expression changes occur in response to severe burns, which may underlie chronic alterations in physiological pathways. Identifying the key altered genes may reveal potential therapeutic targets for mitigating the effects of severe burns.


2021 ◽  
Vol 12 ◽  
Author(s):  
Facai Zhang ◽  
Xiaoming Wang ◽  
Yunjin Bai ◽  
Huan Hu ◽  
Yubo Yang ◽  
...  

ObjectivesThis study aimed to develop and validate a hypoxia signature for predicting survival outcomes in patients with bladder cancer.MethodsWe downloaded the RNA sequence and the clinicopathologic data of the patients with bladder cancer from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository?facetTab=files) and the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) databases. Hypoxia genes were retrieved from the Molecular Signatures Database (https://www.gsea-msigdb.org/gsea/msigdb/index.jsp). Differentially expressed hypoxia-related genes were screened by univariate Cox regression analysis and Lasso regression analysis. Then, the selected genes constituted the hypoxia signature and were included in multivariate Cox regression to generate the risk scores. After that, we evaluate the predictive performance of this signature by multiple receiver operating characteristic (ROC) curves. The CIBERSORT tool was applied to investigate the relationship between the hypoxia signature and the immune cell infiltration, and the maftool was used to summarize and analyze the mutational data. Gene-set enrichment analysis (GSEA) was used to investigate the related signaling pathways of differentially expressed genes in both risk groups. Furthermore, we developed a model and presented it with a nomogram to predict survival outcomes in patients with bladder cancer.ResultsEight genes (AKAP12, ALDOB, CASP6, DTNA, HS3ST1, JUN, KDELR3, and STC1) were included in the hypoxia signature. The patients with higher risk scores showed worse overall survival time than the ones with lower risk scores in the training set (TCGA) and two external validation sets (GSE13507 and GSE32548). Immune infiltration analysis showed that two types of immune cells (M0 and M1 macrophages) had a significant infiltration in the high-risk group. Tumor mutation burden (TMB) analysis showed that the risk scores between the wild types and the mutation types of TP53, MUC16, RB1, and FGFR3 were significantly different. Gene-Set Enrichment Analysis (GSEA) showed that immune or cancer-associated pathways belonged to the high-risk groups and metabolism-related signal pathways were enriched into the low-risk group. Finally, we constructed a predictive model with risk score, age, and stage and validated its performance in GEO datasets.ConclusionWe successfully constructed and validated a novel hypoxia signature in bladder cancer, which could accurately predict patients’ prognosis.


2021 ◽  
Author(s):  
Jian Li ◽  
Yang Liu ◽  
Fei Liu ◽  
Qiang Tian ◽  
Baojiang Li ◽  
...  

Abstract It is well known that Breast cancer is a heterogeneous disease.Although the current recurrence and mortality rate have been greatly improved, many people still suffer relapse and metastasis.Metabolic reprograming is currently considered to be a new hallmark of cancer.Therefore,in this study, we comprehensively analyzed the prognostic effect of metabolic-related gene signatures in breast cancer and its relationship with the immune microenvironment.We constructed a novel metabolic-related gene signature containing 6 genes to distinguish between high and low risk groups by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression, and validated its robustness and accuracy through multiple databases.The metabolic gene signature may be an independent risk factor for BC both in the training and the testing set,the nomogram has a moderately accurate performance,and the C index was 0.757 and 0.728 respectively.The signature can reveal metabolic characteristics based on gene set enrichment analysis and at the same time monitor the status of TME.This gene signature can be used as a promising independent prognostic marker for BC patients, and can indicate the current status of TME, providing more clues for exploring new diagnostic and treatment strategies.


2020 ◽  
Author(s):  
Binbin Cui ◽  
Fuqiang Zhao ◽  
Yanlong Liu ◽  
Xinyue Gu ◽  
Bomiao Zhang ◽  
...  

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.


2020 ◽  
Author(s):  
Xiaomei Lei ◽  
Zhijun Feng ◽  
Xiaojun Wang ◽  
Xiaodong He

Abstract Background. Exploring alterations in the host transcriptome following SARS-CoV-2 infection is not only highly warranted to help us understand molecular mechanisms of the disease, but also provide new prospective for screening effective antiviral drugs, finding new therapeutic targets, and evaluating the risk of systemic inflammatory response syndrome (SIRS) early.Methods. We downloaded three gene expression matrix files from the Gene Expression Omnibus (GEO) database, and extracted the gene expression data of the SARS-CoV-2 infection and non-infection in human samples and different cell line samples, and then performed gene set enrichment analysis (GSEA), respectively. Thereafter, we integrated the results of GSEA and obtained co-enriched gene sets and co-core genes in three various microarray data. Finally, we also constructed a protein-protein interaction (PPI) network and molecular modules for co-core genes and performed Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis for the genes from modules to clarify their possible biological processes and underlying signaling pathway. Results. A total of 11 co-enriched gene sets were identified from the three various microarray data. Among them, 10 gene sets were activated, and involved in immune response and inflammatory reaction. 1 gene set was suppressed, and participated in cell cycle. The analysis of molecular modules showed that 2 modules might play a vital role in the pathogenic process of SARS-CoV-2 infection. The KEGG enrichment analysis showed that genes from module one enriched in signaling pathways related to inflammation, but genes from module two enriched in signaling of cell cycle and DNA replication. Particularly, necroptosis signaling, a newly identified type of programmed cell death that differed from apoptosis, was also determined in our findings. Additionally, for patients with SARS-CoV-2 infection, genes from module one showed a relatively high-level expression while genes from module two showed low-level. Conclusions. We identified two molecular modules were used to assess severity and predict the prognosis of the patients with SARS-CoV-2 infection. In addition, these results provide a unique opportunity to explore more molecular pathways as new potential targets on therapy in COVID 19.


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