scholarly journals A novel survival model based on a Ferroptosis-related gene signature for predicting overall survival in bladder cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yingchun Liang ◽  
Fangdie Ye ◽  
Chenyang Xu ◽  
Lujia Zou ◽  
Yun Hu ◽  
...  

Abstract Background The effective treatment and prognosis prediction of bladder cancer (BLCA) remains a medical problem. Ferroptosis is an iron-dependent form of programmed cell death. Ferroptosis is closely related to tumour occurrence and progression, but the prognostic value of ferroptosis-related genes (FRGs) in BLCA remains to be further clarified. In this study, we identified an FRG signature with potential prognostic value for patients with BLCA. Methods The corresponding clinical data and mRNA expression profiles of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression was used to extract FRGs related to survival time, and a Cox regression model was used to construct a multigene signature. Both principal component analysis (PCA) and single-sample gene set enrichment analysis (ssGSEA) were performed for functional annotation. Results Clinical traits were combined with FRGs, and 15 prognosis-related FRGs were identified by Cox regression. High expression of CISD1, GCLM, CRYAB, SLC7A11, TFRC, ACACA, ZEB1, SQLE, FADS2, ABCC1, G6PD and PGD was related to poor survival in BLCA patients. Multivariate Cox regression was used to construct a prognostic model with 7 FRGs that divided patients into two risk groups. Compared with that in the low-risk group, the overall survival (OS) of patients in the high-risk group was significantly lower (P < 0.001). In multivariate regression analysis, the risk score was shown to be an independent predictor of OS (HR = 1.772, P < 0.01). Receiver operating characteristic (ROC) curve analysis verified the predictive ability of the model. In addition, the two risk groups displayed different immune statuses in ssGSEA and different distributed patterns in PCA. Conclusion Our research suggests that a new gene model related to ferroptosis can be applied for the prognosis prediction of BLCA. Targeting FRGs may be a treatment option for BLCA.

2021 ◽  
Author(s):  
Yingchun Liang ◽  
Fangdie Ye ◽  
Chenyang Xu ◽  
Lujia Zou ◽  
Yun Hu ◽  
...  

Abstract Background: The effective treatment and prognosis prediction of bladder cancer(BLCA) remains a medical problem. Ferroptosis is an iron-dependent form of programmed cell death. Ferroptosis are closely related to tumor occurrence and progression, but the prognostic value of ferroptosis-related genes (FRGs) in BLCA remains to be further clarified. In this study, we identified a FRGs signature with potential prognostic value for patients with BLCA. Methods: The corresponding clinical data and the mRNA expression profile of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression was used to extract FRGs related to survival time, Cox regression model was applied to construct a multigene signature. Both principal component analysis (PCA) and single-sample gene set enrichment analysis (ssGSEA) were performed for functional annotation. Results: Clinical traits were combined with FRGs, so that 15 prognostic-related FRGs were identified by Cox regression. High expression of CISD1, GCLM, CRYAB, SLC7A11, TFRC, ACACA, ZEB1, SQLE, FADS2, ABCC1, G6PD and PGD are related to poor survival rates of BLCA patients. Multivariate Cox regression constructed a prognostic model with 7 FRGs and divided patients into two risk groups. Compared with the low-risk group, the overall survival(OS) of patients in the high-risk group was significantly lower (P <0.001). In multivariate regression analysis, the risk score was shown to be an independent predictor of OS (HR> 1, P <0.01). ROC curve analysis verified the predictive ability of the model. In addition, the two risk groups displayed different immune statuses in the ssGSEA and different distributed patterns in PCA. Conclusion: Our research suggests that a new gene model related to ferroptosis can be applied for the prognosis prediction of BLCA. Targeting FRGs may be a treatment option for BLCA.


2021 ◽  
Author(s):  
Cheng Lijing ◽  
Yuan Meiling ◽  
Li Shu ◽  
Chen Junjing ◽  
Zhong Shupeng ◽  
...  

Abstract Background: Brain glioblastoma (GBM) is the most common primary malignant tumor of intracranial tumors. The prognosis of this disease is extremely poor. While the introduction of IFN-β regimen in the treatment of gliomas has significantly improved the outcome of patients, the underlying mechanism remains to be elucidated. Materials and methods: mRNA expression profiles and clinicopathological data were downloaded from TCGA-GBM and GSE83300 data set from the GEO. Univariate Cox regression analysis and lasso Cox regression model established a novel four‐gene IFN-β signature (including PRDX1, SEC61B, XRCC5, and BCL2L2) for GBM prognosis prediction. Further, GBM samples (n=50) and normal brain tissues (n=50) were then used for real-time polymerase chain reaction (PCR) experiments. Gene Set Enrichment Analyses (GSEA) was performed to further understand the underlying molecular mechanisms. Pearson correlation was applied to calculate the correlation between the lncRNAs and IFN-β associated genes. A lncRNA with a correlation coefficient |R2| > 0.3 and P < 0.05 was considered to be an IFN-β associated lncRNA.Results: Patients in the high‐risk group shown significantly poorer survival than patients in the low‐risk group. The signature was found to be an independent prognostic factor for GBM survival. Furthermore, GSEA revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust four‐gene IFN-β signature for GBM prognosis prediction. The signature might contain potential biomarkers for metabolic therapy and treatment response prediction in GBM.Conclusions: Our study established a novel IFN-β associated genes signature to predict overall survival of GBM, which may help in clinical decision making for individual treatment.


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.


Author(s):  
Dongyan Zhao ◽  
Xizhen Sun ◽  
Sidan Long ◽  
Shukun Yao

AbstractAimLong non-coding RNAs (lncRNAs) have been identified to regulate cancers by controlling the process of autophagy and by mediating the post-transcriptional and transcriptional regulation of autophagy-related genes. This study aimed to investigate the potential prognostic role of autophagy-associated lncRNAs in colorectal cancer (CRC) patients.MethodsLncRNA expression profiles and the corresponding clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, autophagy-related lncRNAs were identified by Pearson correlation test. Univariate Cox regression analysis and the least absolute shrinkage and selection operator analysis (LASSO) Cox regression model were performed to construct the prognostic gene signature. Gene set enrichment analysis (GSEA) was used to further clarify the underlying molecular mechanisms.ResultsWe obtained 210 autophagy-related genes from the whole dataset and found 1187 lncRNAs that were correlated with the autophagy-related genes. Using Univariate and LASSO Cox regression analyses, eight lncRNAs were screened to establish an eight-lncRNA signature, based on which patients were divided into the low-risk and high-risk group. Patients’ overall survival was found to be significantly worse in the high-risk group compared to that in the low-risk group (log-rank p = 2.731E-06). ROC analysis showed that this signature had better prognostic accuracy than TNM stage, as indicated by the area under the curve. Furthermore, GSEA demonstrated that this signature was involved in many cancer-related pathways, including TGF-β, p53, mTOR and WNT signaling pathway.ConclusionsOur study constructed a novel signature from eight autophagy-related lncRNAs to predict the overall survival of CRC, which could assistant clinicians in making individualized treatment.


2022 ◽  
Author(s):  
Thongher Lia ◽  
Yanxiang Shao ◽  
Parbatraj Regmi ◽  
Xiang Li

Bladder cancer is one of the highly heterogeneous disorders accompanied by a poor prognosis. This study aimed to construct a model based on pyroptosis‑related lncRNA to evaluate the potential prognostic application in bladder cancer. The mRNA expression profiles of bladder cancer patients and corresponding clinical data were downloaded from the public database from The Cancer Genome Atlas (TCGA). Pyroptosis‑related lncRNAs were identified by utilizing a co-expression network of Pyroptosis‑related genes and lncRNAs. The lncRNA was further screened by univariate Cox regression analysis. Finally, 8 pyroptosis-related lncRNA markers were established using Lasso regression and multivariate Cox regression analysis. Patients were separated into high and low-risk groups based on the performance value of the median risk score. Patients in the high-risk group had significantly poorer overall survival (OS) than those in the low-risk group (p &lt; 0.001), and In multivariate Cox regression analysis, the risk score was an independent predictive factor of OS ( HR&gt;1, P&lt;0.01). The area under the curve (AUC) of the 3- and 5-year OS in the receiver operating characteristic (ROC) curve were 0.742 and 0.739 respectively. In conclusion, these 8 pyroptosis-related lncRNA and their markers may be potential molecular markers and therapeutic targets for bladder cancer patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lei Zhu ◽  
Fugui Yang ◽  
Lingwei Wang ◽  
Lin Dong ◽  
Zhiyuan Huang ◽  
...  

Abstract Background Ferroptosis is a recently recognized non-apoptotic cell death that is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in esophageal adenocarcinoma (EAC) remains unclear. This study aims to explore the ferroptosis-related genes (FRG) expression profiles and their prognostic values in EAC. Methods The FRG data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate cox regressions were used to identify the prognostic FRG, and the predictive ROC model was established using the independent risk factors. GO and KEGG enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and TIMER database. Finally, SDG were verified in clinical EAC specimens and normal esophageal mucosal tissues. Results Twenty-eight significantly different FRG were screened from 78 EAC and 9 normal tissues. Enrichment analyses showed these SDG were mainly related to the iron-related pathways and metabolisms of ferroptosis. Gene network demonstrated the TP53, G6PD, NFE2L2 and PTGS2 were the hub genes in the biology of ferroptosis. Cox regression analyses demonstrated four FRG (CARS1, GCLM, GLS2 and EMC2) had prognostic values for overall survival (OS) (all P < 0.05). ROC curve showed better predictive ability using the risk score (AUC = 0.744). Immune cell enrichment analysis demonstrated that the types of immune cells and their expression levels in the high-risk group were significant different with those in the low-risk group (all P < 0.05). The experimental results confirmed the ALOX5, NOX1 were upregulated and the MT1G was downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P < 0.05). Conclusions We identified differently expressed ferroptosis-related genes that may involve in EAC. These genes have significant values in predicting the patients’ OS and targeting ferroptosis may be an alternative for therapy. Further studies are necessary to verify these results of our study.


2021 ◽  
Author(s):  
Liyuan Wu ◽  
Feiya Yang ◽  
Nianzeng Xing

Abstract Background Bladder cancer (BC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis is related to a variety of biological pathways, including those involved in the metabolism of amino acids, lipids, and iron. However, the prognostic value of ferroptosis-related genes in BC remains to be further elucidated. Methods In this study, the mRNA expression profiles and corresponding clinical data of BC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature and validated it. Results Our results showed 12 differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted P< 0.05). A 9-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group (P < 0.001). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1, P< 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups, especially in humoral immune response process. Conclusion In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in BC. Targeting ferroptosis may be a therapeutic alternative for BC.


2020 ◽  
Author(s):  
Andi Ma ◽  
Yukai Sun ◽  
Racheal O. Ogbodu ◽  
Ling Xiao ◽  
Haibing Deng ◽  
...  

Abstract Background: It is well known that long non-coding RNAs (lncRNAs) play a vital role in cancer. We aimed to explore the prognostic value of potential immune-related lncRNAs in hepatocellular carcinoma (HCC). Methods: Validated the established lncRNA signature of 343 patients with HCC from The Cancer Genome Atlas (TCGA) and 81 samples from Gene Expression Omnibus (GEO). Immune-related lncRNAs for HCC prognosis were evaluated using Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. LASSO analysis was performed to calculate a risk score formula to explore the difference in overall survival between high- and low-risk groups in TCGA, which was verified using GEO, Gene Ontology (GO), and pathway-enrichment analysis. These analyses were used to identify the function of screened genes and construct a co-expression network of these genes. Results: Using computational difference algorithms and lasso Cox regression analysis, the differentially expressed and survival-related immune-related genes (IRGs) among patients with HCC were established as five novel immune-related lncRNA signatures (AC099850.3, AL031985.3, PRRT3-AS1, AC023157.3, MSC-AS1). Patients in the low‐risk group showed significantly better survival than patients in the high‐risk group ( P = 3.033e−05). The signature identified can be an effective prognostic factor to predict patient survival. The nomogram showed some clinical net benefits predicted by overall survival. In order to explore its underlying mechanism, several methods of enrichment were elucidated using Gene Set Enrichment Analysis. Conclusion: Identifying five immune-related lncRNA signatures has important clinical implications for predicting patient outcome and guiding tailored therapy for patients with HCC with further prospective validation.


2020 ◽  
Author(s):  
Lei Zhu ◽  
Fugui Yang ◽  
Lingwei Wang ◽  
Lin Dong ◽  
Zhiyuan Huang ◽  
...  

Abstract Background Ferroptosis is a recently recognized non-apoptotic cell death that is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in esophageal adenocarcinoma (EAC) remains unclear. The aim of this study was to explore the ferroptosis-related genes (FRG) expression profiles and their prognostic values in EAC.Methods The FRG data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate cox regressions were used to identify the prognostic FRG, and the predictive ROC model was established using the independent risk factors. GO and KEGG enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA). Finally, significantly different genes were verified in our clinical EAC specimens and normal esophageal mucosal tissues.Results: Twenty-eight significantly different FRG were screened from 78 EAC and 9 normal tissues. GO and KEGG enrichments showed these SDG were mainly related to the iron-related pathways and metabolisms of ferroptosis. Gene network demonstrated the TP53, G6PD, NFE2L2 and PTGS2 were the hub genes in the biology of ferroptosis. Cox regression analyses demonstrated four FRG (CARS1, GCLM, GLS2 and EMC2) had prognostic values for overall survival (OS) (all P<0.001). ROC curves showed better efficacy to predict survival using the risk score (AUC=0.744). Immune cell enrichment analysis demonstrated that the types of immune cells and their expression levels in the high-risk group were significant different with those in the low-risk group (all P<0.05). The experimental results confirmed the ALOX5, NOX1 were upregulated and the MT1G was downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P<0.05).Conclusions: We identified differently expressed ferroptosis-related genes that may involve in the process in EAC. These genes have significant values in predicting the patients’ OS and targeting ferroptosis may be an alternative for therapy. Further studies are necessary to verify these results of our study.


2021 ◽  
Author(s):  
Yuhao Zhang ◽  
Jiaxin Zhang ◽  
Fengxian Wei ◽  
Haodong Zhang ◽  
Dongdong Wang ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC), which carries a very bad prognosis, is a common malignant tumor worldwide. This study aim to identify a pyroptosis-related long non-coding RNA(pyLncRNA) prognostic signature in HCC by integrated bioinformatics analysis. Methods: All expression profiles of HCC were obtained from The Cancer Genome Atlas (TCGA) and pyroptosis-related genes were from the GSEA website. After identified differentially expressed pyLncRNAs, univariate Cox regression and Lasso analysis were used to identify a pyroptosis-related LncRNAs prognositic signature(py-LPS). Internal validation was used to validate the prognostic value of the py-LPS via the Kaplan-Meier(K-M) curve and receiver operating characteristic(ROC) curve. Additional, we established the nomogram and analyzed the correlation between the signature and immune immune infiltration as well as clinical treatment. Result: 7 pyLncRNAs were established the signature for HCC prognosis. K-M curves exhibited the low risk group presented a markedly longer OS than the high. Clinical subgroups analysis based age, gender, grade and stage yielded the similar results. The signature had an independent prognostic value for HCC(p<0.001). Nomogram estimated one-, three- and five-year survival were 0.777, 0.741 and 0.709. Then, gene set enrichment analysis(GSEA) demostrated significant pathways. Futhermore, we found immune cell infiltration and immunotherapy targets was associated with the signature,which could provided clinical recommendations for chemotherapy.Conclusion: In this study, a novel pyroptosis-related LncRNAs porgnostic signature of HCC, correlated with immune infiltration, could predict the survival of HCC patients and give suggestions for clinical treatment.


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