scholarly journals A robust eleven-genes prognostic model can predict overall survival in bladder cancer patients based on five cohorts

2020 ◽  
Author(s):  
Jiaxing Lin ◽  
Jieping Yang ◽  
Xiao Xu ◽  
Yutao Wang ◽  
Meng Yu ◽  
...  

Abstract Background: Bladder cancer is the tenth most common cancer globally, but existing biomarkers and prognostic models are limited. Method: In this study, we used four bladder cancer cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases to perform univariate Cox regression analysis to identify common prognostic genes. We used the least absolute shrinkage and selection operator regression to construct a prognostic Cox model. Kaplan-Meier analysis, receiver operating characteristic curve, and univariate / multivariate Cox analysis were used to evaluate the prognostic model for the four cohorts. Finally, a co-expression network, CIBERSORT, and ESTIMATE algorithm were used to explore the mechanism related to the model. Results: A total of 11 genes were identified from the four cohorts to construct the prognostic model, including eight risk genes (SERPINE2, PRR11, DSEL, DNM1, COMP, ELOVL4, RTKN, and MAPK12) and three protective genes (FABP6, C16orf74, and TNK1). The 11-genes model could stratify the risk of patients in all five cohorts, and the prognosis was worse in the group with a high-risk score. The area under the curve values of the five cohorts in the first year are all greater than 0.65. Furthermore, this model's predictive ability is stronger than that of age, gender, grade, and T stage. Through the weighted co-expression network analysis, the gene module related to the model was found, and the key genes in this module were mainly enriched in the tumor microenvironment. B cell memory showed low infiltration in high-risk patients. Furthermore, in the case of low B cell memory infiltration and high-risk score, the prognosis of the patients was the worst. Conclusion: The proposed eleven-genes model is a promising biomarker for estimating overall survival in bladder cancer. This model can be used to stratify the risk of bladder cancer patients, which is beneficial to the realization of individualized treatment.

2020 ◽  
Author(s):  
Jiaxing Lin ◽  
Jieping Yang ◽  
Xiao Xu ◽  
Yutao Wang ◽  
Meng Yu ◽  
...  

Abstract Background: Bladder cancer is the tenth most common cancer globally, but existing biomarkers and prognostic models are limited. Method: In this study, we used four bladder cancer cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases to perform univariate Cox regression analysis to identify common prognostic genes. We used the least absolute shrinkage and selection operator regression to construct a prognostic Cox model. Kaplan-Meier analysis, receiver operating characteristic curve, and univariate / multivariate Cox analysis were used to evaluate the prognostic model for the four cohorts. Finally, a co-expression network, CIBERSORT, and ESTIMATE algorithm were used to explore the mechanism related to the model.Results: A total of 11 genes were identified from the four cohorts to construct the prognostic model, including eight risk genes (SERPINE2, PRR11, DSEL, DNM1, COMP, ELOVL4, RTKN, and MAPK12) and three protective genes (FABP6, C16orf74, and TNK1). The 11-genes model could stratify the risk of patients in all five cohorts, and the prognosis was worse in the group with a high-risk score. The area under the curve values of the five cohorts in the first year are all greater than 0.65. Furthermore, this model's predictive ability is stronger than that of age, gender, grade, and T stage. Through the weighted co-expression network analysis, the gene module related to the model was found, and the key genes in this module were mainly enriched in the tumor microenvironment. B cell memory showed low infiltration in high-risk patients. Furthermore, in the case of low B cell memory infiltration and high-risk score, the prognosis of the patients was the worst.Conclusion: The proposed eleven-genes model is a promising biomarker for estimating overall survival in bladder cancer. This model can be used to stratify the risk of bladder cancer patients, which is beneficial to the realization of individualized treatment.


Author(s):  
Jiaxing Lin ◽  
Jieping Yang ◽  
Xiao Xu ◽  
Yutao Wang ◽  
Meng Yu ◽  
...  

Abstract Background: Bladder cancer is the tenth most common cancer in the world, but existing biomarkers and prognostic models are limited.Method: In this study, we used four bladder cancer cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases to perform univariate Cox regression analysis to identify common prognostic genes. We used selected genes to construct a prognostic model. Kaplan-Meier analysis, Receiver Operating Characteristic curve, and univariate and multivariate Cox analysis were used to evaluate the prognostic model for the four cohorts. Finally, a co-expression network, CIBERSORT, and ESTIMATE algorithm were used to explore the mechanism related to the model.Results: A total of 11 genes were identified from the four cohorts to construct the prognostic model, including eight risk genes (SERPINE2, PRR11, DSEL, DNM1, COMP, ELOVL4, RTKN, and MAPK12) and three protective genes (FABP6, C16orf74, and TNK1). The model and the 11 genes have excellent performance in predicting overall survival and have been confirmed in 5 cohorts. The model's predictive ability is stronger than other clinical features and has practical significance in clinical application.Through the analysis of the weighted co-expression network, the gene module related to the model was found, and the key genes in this module were mainly enriched in the items related to the tumor microenvironment. When comparing the level of immune cell infiltration in high-risk samples, B cell memory showed low infiltration in high-risk patients. Furthermore, in the case of low B cell memory infiltration and high-risk score, the prognosis of the patients was the worst.Conclusion: The model we developed has strong stability and good performance and can stratify the risk of bladder cancer patients, to achieve individualized treatment.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qian Yan ◽  
Wenjiang Zheng ◽  
Boqing Wang ◽  
Baoqian Ye ◽  
Huiyan Luo ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xu Wang ◽  
Yuanmin Xu ◽  
Ting Li ◽  
Bo Chen ◽  
Wenqi Yang

Abstract Background Autophagy is an orderly catabolic process for degrading and removing unnecessary or dysfunctional cellular components such as proteins and organelles. Although autophagy is known to play an important role in various types of cancer, the effects of autophagy-related genes (ARGs) on colon cancer have not been well studied. Methods Expression profiles from ARGs in 457 colon cancer patients were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed ARGs and ARGs related to overall patient survival were identified. Cox proportional-hazard models were used to investigate the association between ARG expression profiles and patient prognosis. Results Twenty ARGs were significantly associated with the overall survival of colon cancer patients. Five of these ARGs had a mutation rate ≥ 3%. Patients were divided into high-risk and low-risk groups based on Cox regression analysis of 8 ARGs. Low-risk patients had a significantly longer survival time than high-risk patients (p < 0.001). Univariate and multivariate Cox regression analysis showed that the resulting risk score, which was associated with infiltration depth and metastasis, could be an independent predictor of patient survival. A nomogram was established to predict 1-, 3-, and 5-year survival of colon cancer patients based on 5 independent prognosis factors, including the risk score. The prognostic nomogram with online webserver was more effective and convenient to provide information for researchers and clinicians. Conclusion The 8 ARGs can be used to predict the prognosis of patients and provide information for their individualized treatment.


2021 ◽  
Vol 2021 ◽  
pp. 1-26
Author(s):  
Xiao-Jie Liang ◽  
Rui-ying Fu ◽  
He-nan Wang ◽  
Jing Yang ◽  
Na Yao ◽  
...  

Background. Diffuse large B cell lymphoma (DLBCL) is a life-threatening malignant tumor characterized by heterogeneous clinical, phenotypic, and molecular manifestations. Given the association between immunity and tumors, identifying a suitable immune biomarker could improve DLBCL diagnosis. Methods. We systematically searched for DLBCL gene expression microarray datasets from the GEO database. Immune-related genes (IRGs) were obtained from the ImmPort database, and 318 transcription factor (TF) targets in cancer were retrieved from the Cistrome Cancer database. An immune-related classifier for DLBCL prognosis was constructed using Cox regression and LASSO analysis. To assess differences in overall survival between the low- and high-risk groups, we analyzed the tumor microenvironment (TME) and immune infiltration in DLBCL using the ESTIMATE and CIBERSORT algorithms. WGCNA was applied to study the molecular mechanisms explaining the clinical significance of our immune-related classifier and TFs. Results. Eighteen IRGs were selected to construct the classifier. The multi-IRG classifier showed powerful predictive ability. Patients with a high-risk score had poor survival. Based on the AUC for three- and five-year survival, the classifier exhibited better predictive power than clinical data. Discrepancies in overall survival between the low- and high-risk score groups might be explained by differences in immune infiltration, TME, and transcriptional regulation. Conclusions. Our study describes a novel prognostic IRG classifier with strong predictive power in DLBCL. Our findings provide valuable guidance for further analysis of DLBCL pathogenesis and clinical treatment.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Huamei Tang ◽  
Lijuan Kan ◽  
Tong Ou ◽  
Dayang Chen ◽  
Xiaowen Dou ◽  
...  

Abstract Background: Bladder cancer is one of the most common malignancies. So far, no effective biomarker for bladder cancer prognosis has been identified. Aberrant DNA methylation is frequently observed in the bladder cancer and holds considerable promise as a biomarker for predicting the overall survival (OS) of patients. Materials and methods: We downloaded the DNA methylation and transcriptome data for bladder cancer from The Cancer Genome Atlas (TCGA), a public database, screened hypo-methylated and up-regulated genes, similarly, hyper-methylation with low expression genes, then retrieved the relevant methylation sites. Cox regression analysis was used to identify a nine-methylation site signature of a training group. Predictive ability was validated in a test group by receiver operating characteristic (ROC) analysis. Results: We identified nine bladder cancer-specific methylation sites as potential prognostic biomarkers and established a risk score system based on the methylation site signature to evaluate the OS. The performance of the signature was accurate, with area under curve was 0.73 in the training group and 0.71 in the test group. Taking clinical features into consideration, we constructed a nomogram consisting of the nine-methylation site signature and patients’ clinical variables, and found that the signature was an independent risk factor. Conclusions: Overall, the significant nine methylation sites could be novel prediction biomarkers, which could aid in treatment and also predict the overall survival likelihoods of bladder cancer patients.


Author(s):  
Dawei Zhou ◽  
Junchen Wan ◽  
Jiang Luo ◽  
Yuhao Tao

Background: Liver cancer is one of the most common diseases in the world. At present, the mechanism of autophagy genes in liver cancer is not very clear. Therefore, it is meaningful to study the role and prognostic value of autophagy genes in liver cancer. Objective: The purpose of this study is to conduct a bioinformatics analysis of autophagy genes related to primary liver cancer to establish a prognostic model of primary liver cancer based on autophagy genes. Results: Through difference analysis, 31 differential autophagy genes were screened out and then analyzed by GO and KEGG analysis. At the same time, we built a PPI network. To optimize the evaluation of the prognosis of liver cancer patients, we integrated multiple autophagy genes to establish a prognostic model. By using univariate cox regression analysis, 15 autophagy genes related to prognosis were screened out. Then we included these 15 genes into the Least Absolute Shrinkage and Selection Operator (LASSO), and performed multi-factor cox regression analysis on the 9 selected genes to construct a prognostic model. The risk score of each patient was calculated based on 4 genes(BIRC5, HSP8, SQSTM1, and TMEM74) which participated in the establishing of the model, then the patients were divided into high-risk groups and low-risk groups. In the multivariate cox regression analysis, the risk score was the independent prognostic factors (HR=1.872, 95%CI=1.544-2.196, P<0.001). Survival analysis showed that the survival time of the low-risk group was significantly longer than that of the high-risk group. Combining clinical characteristics and autophagy genes, we constructed a nomogram for predicting prognosis. The external dataset GSE14520 proved that the nomogram has a good prediction for individual patients with primary liver cancer. Conclusion: This study provided potential autophagy-related markers for liver cancer patients to predict their prognosis and revealed part of the molecular mechanism of liver cancer autophagy. At the same time, the certain gene pathways and protein pathways related to autophagy may provide some inspiration for the development of anticancer drugs.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Liwei Wang ◽  
Jiazhong Shi ◽  
Yaqin Huang ◽  
Sha Liu ◽  
Jingqi Zhang ◽  
...  

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.


2020 ◽  
Author(s):  
Xu Wang ◽  
Yuanmin Xu ◽  
Ting Li ◽  
Bo Chen ◽  
Wenqi Yang

Abstract Background: Autophagy is an orderly catabolic process for degrading and removing unnecessary or dysfunctional cellular components such as proteins and organelles. Although autophagy is known to play an important role in various types of cancer, the effects of autophagy-related genes (ARGs) on colon cancer have not been well studied.Methods: Expression profiles from ARGs in 457 colon cancer patients were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed ARGs and ARGs related to overall patient survival were identified. Cox proportional-hazards models were used to investigate the association between ARG expression profiles and patient prognosis.Results: 20 ARGs were significantly associated with overall survival of colon cancer patients. Five of these ARGs had a mutation rate ≥3%. Patients were divided into high-risk and low-risk groups based on Cox regression analysis of 8 ARGs. Low-risk patients had a significantly longer survival time than high-risk patients (p<0.001). Univariate and multivariate Cox regression analysis showed that the resulting risk score, which was associated with infiltration depth and metastasis, could be an independent predictor of patient survival. A nomogram was established to predict 3- and 5-year survival of colon cancer patients based on 5 independent prognosis factors, including the risk score. The prognostic nomogram with online webserver was more effective and convenient to provide information for researchers and clinicians.Conclusion: The 8 ARGs can be used to predict the prognosis of patients and provide information for their individualized treatment.


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