scholarly journals The construction and validation of an RNA binding protein-related prognostic model for bladder cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fengxia Chen ◽  
Qingqing Wang ◽  
Yunfeng Zhou

Abstract Background RNA-binding proteins (RBPs) play crucial and multifaceted roles in post-transcriptional regulation. While RBPs dysregulation is involved in tumorigenesis and progression, little is known about the role of RBPs in bladder cancer (BLCA) prognosis. This study aimed to establish a prognostic model based on the prognosis-related RBPs to predict the survival of BLCA patients. Methods We downloaded BLCA RNA sequence data from The Cancer Genome Atlas (TCGA) database and identified RBPs differentially expressed between tumour and normal tissues. Then, functional enrichment analysis of these differentially expressed RBPs was conducted. Independent prognosis-associated RBPs were identified by univariable and multivariable Cox regression analyses to construct a risk score model. Subsequently, Kaplan–Meier and receiver operating characteristic curves were plotted to assess the performance of this prognostic model. Finally, a nomogram was established followed by the validation of its prognostic value and expression of the hub RBPs. Results The 385 differentially expressed RBPs were identified included 218 and 167 upregulated and downregulated RBPs, respectively. The eight independent prognosis-associated RBPs (EFTUD2, GEMIN7, OAS1, APOBEC3H, TRIM71, DARS2, YTHDC1, and RBMS3) were then used to construct a prognostic prediction model. An in-depth analysis showed lower overall survival (OS) in patients in the high-risk subgroup compared to that in patients in the low-risk subgroup according to the prognostic model. The area under the curve of the time-dependent receiver operator characteristic (ROC) curve were 0.795 and 0.669 for the TCGA training and test datasets, respectively, showing a moderate predictive discrimination of the prognostic model. A nomogram was established, which showed a favourable predictive value for the prognosis of BLCA. Conclusions We developed and validated the performance of a prognostic model for BLCA that might facilitate the development of new biomarkers for the prognostic assessment of BLCA patients.

2020 ◽  
Author(s):  
Xinhong Liu ◽  
Fang Tan ◽  
Xingyao Long ◽  
Ruokun Yi ◽  
Dingyi Yang ◽  
...  

Abstract Background RNA binding proteins (RBPs) play an important role in a variety of cancers. However, the role of RBPs in colorectal adenocarcinoma (COAD) has not been studied. Integrated analysis of RBPs will provide a better understanding of disease genesis and new insights into COAD treatment. Methods The gene expression data and corresponding clinical information for COAD were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis was used to screen for RBPs associated with COAD recurrence, and multivariate Cox proportional hazards regression analyses were used to identify genes that were associated with COAD recurrence. A nomogram was constructed to predict the recurrence of COAD, and a receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of the prediction models. The Human Protein Atlas database was used in prediction models to confirm the expression of key genes in COAD patients. Result A total of 177 differentially expressed RBPs was obtained, comprising 123 upregulated and 54 downregulated. GO and KEGG enrichment analysis showed that the differentially expressed RBPs were mainly related to mRNA metabolism, RNA processing and translation regulation. Seven RBP genes (TDRD6, POP1, TDRD7, PPARGC1A, LIN28B, LRRFIP2 and PNLDC1) were identified as prognosis-associated genes and were used to construct the prognostic model. Conclusion We constructed a COAD prognostic model through bioinformatics analysis, which indicated that prognostic model RBPs have a potential role in the diagnosis and prognosis of COAD. Moreover, the nomogram can effectively predict the 1-year, 3-year, and 5-year survival rate for COAD patients.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Min Wang ◽  
Shan Huang ◽  
Zefeng Chen ◽  
Zhiwei Han ◽  
Kezhi Li ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is among the deadliest forms of cancer. While RNA-binding proteins (RBPs) have been shown to be key regulators of oncogenesis and tumor progression, their dysregulation in the context of HCC remains to be fully characterized. Methods Data from the Cancer Genome Atlas - liver HCC (TCGA-LIHC) database were downloaded and analyzed in order to identify RBPs that were differentially expressed in HCC tumors relative to healthy normal tissues. Functional enrichment analyses of these RBPs were then conducted using the GO and KEGG databases to understand their mechanistic roles. Central hub RBPs associated with HCC patient prognosis were then detected through Cox regression analyses, and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, univariate and multivariate Cox regression analyses, and nomograms. Lastly, the relationship between individual hub RBPs and HCC patient overall survival (OS) was evaluated using Kaplan-Meier curves. Finally, find protein-coding genes (PCGs) related to hub RBPs were used to construct a hub RBP-PCG co-expression network. Results In total, we identified 81 RBPs that were differentially expressed in HCC tumors relative to healthy tissues (54 upregulated, 27 downregulated). Seven prognostically-relevant hub RBPs (SMG5, BOP1, LIN28B, RNF17, ANG, LARP1B, and NR0B1) were then used to generate a prognostic model, after which HCC patients were separated into high- and low-risk groups based upon resultant risk score values. In both the training and test datasets, we found that high-risk HCC patients exhibited decreased OS relative to low-risk patients, with time-dependent area under the ROC curve values of 0.801 and 0.676, respectively. This model thus exhibited good prognostic performance. We additionally generated a prognostic nomogram based upon these seven hub RBPs and found that four other genes were significantly correlated with OS. Conclusion We herein identified a seven RBP signature that can reliably be used to predict HCC patient OS, underscoring the prognostic relevance of these genes.


2020 ◽  
Author(s):  
Yingjuan Lu ◽  
Yongcong Yan ◽  
Mo Liu ◽  
Yancan Liang ◽  
Yushan Ye ◽  
...  

Abstract Background: The biological roles and clinical significance of RNA-binding proteins (RBPs) in oral squamous cell carcinoma (OSCC) are not fully understood. We investigated the prognostic value of RBPs in OSCC by several bioinformatic strategies.Methods: OSCC data were obtained from a public online database, the Limma R package was used to identify differentially expressed RBPs, and functional enrichment analysis was performed to elucidate the biological functions of the above RBPs in OSCC. We performed protein-protein interaction (PPI) network and Cox regression analyses to extract prognosis-related hub RBPs. Next, we established and validated a prognostic model based on the hub RBPs by Cox regression and risk score analyses.Results: We found that the differentially expressed RBPs were closely related to the defence response to virus and multiple RNA processes. We obtained ten prognosis-related hub RBPs (ZC3H12D, OAS2, INTS10, ACO1, PCBP4, RNASE3, PTGES3L-AARSD1, RNASE13, DDX4, and PCF11) and effectively predicted the overall survival of OSCC patients. The area under the ROC curve (AUC) of the risk score model was 0.781, suggesting that our model had good prognostic performance. Finally, we built a nomogram integrating the ten RBPs. The internal validation cohort results showed a reliable predictive capability of the nomogram for OSCC.Conclusions: We established a novel ten-RBP-based model for OSCC that could enable precise therapeutic targets in the future.


2020 ◽  
Author(s):  
Min wang ◽  
Shan Huang ◽  
Zefeng Chen ◽  
Zhiwei Han ◽  
Kezhi Li ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC) is among the deadliest forms of cancer. While RNA-binding proteins (RBPs) have been shown to be key regulators of oncogenesis and tumor progression, their dysregulation in the context of HCC remains to be fully characterized. Methods: Data from the Cancer Genome Atlas - liver HCC (TCGA-LIHC) database were downloaded and analyzed in order to identify RBPs that were differentially expressed in HCC tumors relative to healthy normal tissues. Functional enrichment analyses of these RBPs were then conducted using the GO and KEGG databases to understand their mechanistic roles. Central hub RBPs associated with HCC patient prognosis were then detected through Cox regression analyses, and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, univariate and multivariate Cox regression analyses, and nomograms. Lastly, the relationship between individual hub RBPs and HCC patient overall survival (OS) was evaluated using Kaplan-Meier curves. Results: In total, we identified 81 RBPs that were differentially expressed in HCC tumors relative to healthy tissues (54 upregulated, 27 downregulated). Seven prognostically-relevant hub RBPs (SMG5, BOP1, LIN28B, RNF17, ANG, LARP1B, and NR0B1) were then used to generate a prognostic model, after which HCC patients were separated into high- and low-risk groups based upon resultant risk score values. In both the training and test datasets, we found that high-risk HCC patients exhibited decreased OS relative to low-risk patients, with time-dependent area under the ROC curve values of 0.801 and 0.676, respectively. This model thus exhibited good prognostic performance. We additionally generated a prognostic nomogram based upon these seven hub RBPs and found that four other genes were significantly correlated with OS. Conclusion: We herein identified a seven RBP signature that can reliably be used to predict HCC patient OS, underscoring the prognostic relevance of these genes.


2020 ◽  
Author(s):  
Min wang ◽  
Shan Huang ◽  
Zefeng Chen ◽  
Zhiwei Han ◽  
Kezhi Li ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC) is among the deadliest forms of cancer. While RNA-binding proteins (RBPs) have been shown to be key regulators of oncogenesis and tumor progression, their dysregulation in the context of HCC remains to be fully characterized. Methods: Data from the Cancer Genome Atlas - liver HCC (TCGA-LIHC) database were downloaded and analyzed in order to identify RBPs that were differentially expressed in HCC tumors relative to healthy normal tissues. Functional enrichment analyses of these RBPs were then conducted using the GO and KEGG databases to understand their mechanistic roles. Central hub RBPs associated with HCC patient prognosis were then detected through Cox regression analyses, and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, univariate and multivariate Cox regression analyses, and nomograms. Lastly, the relationship between individual hub RBPs and HCC patient overall survival (OS) was evaluated using Kaplan-Meier curves. Finally, find protein-coding genes (PCGs) related to hub RBPs were used to construct a hub RBP-PCG co-expression network.Results: In total, we identified 81 RBPs that were differentially expressed in HCC tumors relative to healthy tissues (54 upregulated, 27 downregulated). Seven prognostically-relevant hub RBPs (SMG5, BOP1, LIN28B, RNF17, ANG, LARP1B, and NR0B1) were then used to generate a prognostic model, after which HCC patients were separated into high- and low-risk groups based upon resultant risk score values. In both the training and test datasets, we found that high-risk HCC patients exhibited decreased OS relative to low-risk patients, with time-dependent area under the ROC curve values of 0.801 and 0.676, respectively. This model thus exhibited good prognostic performance. We additionally generated a prognostic nomogram based upon these seven hub RBPs and found that four other genes were significantly correlated with OS.Conclusion: We herein identified a seven RBP signature that can reliably be used to predict HCC patient OS, underscoring the prognostic relevance of these genes.


2020 ◽  
Author(s):  
Min wang ◽  
Shan Huang ◽  
Zefeng Chen ◽  
Zhiwei Han ◽  
Kezhi Li ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC) is among the deadliest forms of cancer. While RNA-binding proteins (RBPs) have been shown to be key regulators of oncogenesis and tumor progression, their dysregulation in the context of HCC remains to be fully characterized.Methods: Data from the Cancer Genome Atlas - liver HCC (TCGA-LIHC) database were downloaded and analyzed in order to identify RBPs that were differentially expressed in HCC tumors relative to healthy normal tissues. Functional enrichment analyses of these RBPs were then conducted using the GO and KEGG databases to understand their mechanistic roles. Central hub RBPs associated with HCC patient prognosis were then detected through Cox regression analyses, and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, univariate and multivariate Cox regression analyses, and nomograms. Lastly, the relationship between individual hub RBPs and HCC patient overall survival (OS) was evaluated using Kaplan-Meier curves. Finally, find protein-coding genes (PCGs) related to hub RBPs were used to construct a hub RBP-PCG co-expression network.Results: In total, we identified 81 RBPs that were differentially expressed in HCC tumors relative to healthy tissues (54 upregulated, 27 downregulated). Seven prognostically-relevant hub RBPs (SMG5, BOP1, LIN28B, RNF17, ANG, LARP1B, and NR0B1) were then used to generate a prognostic model, after which HCC patients were separated into high- and low-risk groups based upon resultant risk score values. In both the training and test datasets, we found that high-risk HCC patients exhibited decreased OS relative to low-risk patients, with time-dependent area under the ROC curve values of 0.801 and 0.676, respectively. This model thus exhibited good prognostic performance. We additionally generated a prognostic nomogram based upon these seven hub RBPs and found that four other genes were significantly correlated with OS.Conclusion: We herein identified a seven RBP signature that can reliably be used to predict HCC patient OS, underscoring the prognostic relevance of these genes.


2021 ◽  
Author(s):  
Yukun Jia ◽  
Zhan Peng ◽  
Guangye Wang

Abstract Background: RNA binding proteins (RBP) plays an important role in post-transcriptional regulation. Although the dysregulation of RBP expression is closely related to the occurrence and metastasis of a variety of tumors, there are few reports on RBP in endometrial carcinoma (UCEC). This study aims to establish a RBP-related prognostic model of UCEC. Methods: We downloaded UCEC gene expression and clinical information data from the Cancer Genome Atlas (TCGA) and GEO database, and determined RBPs that are differentially expressed between tumors and normal tissues. Then, used functional enrichment analysis to analyze the biological functions of the differentially expressed RBP. Used univariate Cox regression analysis to screen prognostic-related RBP and construct a prognostic model. Subsequently, Kaplan-Meier and recipient operating characteristic (ROC) curves were drawn to evaluate the model. Finally, established a nomogram. Results: This study identified 531 differentially expressed RBPs, including 325 up-regulated and 206 down-regulated RBPs, respectively. Then six independent prognostic-related RBPs (REXO2, MARS2, XPO5, YBX1, YBX2, and CELF4) were used to construct a prognostic model. According to this model, the overall survival (OS) of patients in the high-risk score group was significantly lower than that of the low-risk score group. In the training queue and the test queue, the areas under the ROC curve were 0.799 and 0.669, respectively, showing the moderate predictive value of the model. Conclusion: We have developed and validated the RBP-related prognostic model.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260876
Author(s):  
Jun Yang ◽  
Jiaying Zhou ◽  
Cuili Li ◽  
Shaohua Wang

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.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Zhai ◽  
Bin Zhao ◽  
Yuzhen Wang ◽  
Lina Li ◽  
Jingjin Li ◽  
...  

Abstract Background Lung adenocarcinoma (LUAD) is the most common pathology subtype of lung cancer. In recent years, immunotherapy, targeted therapy and chemotherapeutics conferred a certain curative effects. However, the effect and prognosis of LUAD patients are different, and the efficacy of existing LUAD risk prediction models is unsatisfactory. Methods The Cancer Genome Atlas (TCGA) LUAD dataset was downloaded. The differentially expressed immune genes (DEIGs) were analyzed with edgeR and DESeq2. The prognostic DEIGs were identified by COX regression. Protein-protein interaction (PPI) network was inferred by STRING using prognostic DEIGs with p value< 0.05. The prognostic model based on DEIGs was established using Lasso regression. Immunohistochemistry was used to assess the expression of FERMT2, FKBP3, SMAD9, GATA2, and ITIH4 in 30 cases of LUAD tissues. Results In total,1654 DEIGs were identified, of which 436 genes were prognostic. Gene functional enrichment analysis indicated that the DEIGs were involved in inflammatory pathways. We constructed 4 models using DEIGs. Finally, model 4, which was constructed using the 436 DEIGs performed the best in prognostic predictions, the receiver operating characteristic curve (ROC) was 0.824 for 3 years, 0.838 for 5 years, 0.834 for 10 years. High levels of FERMT2, FKBP3 and low levels of SMAD9, GATA2, ITIH4 expression are related to the poor overall survival in LUAD (p < 0.05). The prognostic model based on DEIGs reflected infiltration by immune cells. Conclusions In our study, we built an optimal prognostic signature for LUAD using DEIGs and verified the expression of selected genes in LUAD. Our result suggests immune signature can be harnessed to obtain prognostic insights.


2021 ◽  
Vol 8 ◽  
Author(s):  
Kezhen Yi ◽  
JingChong Liu ◽  
Yuan Rong ◽  
Cheng Wang ◽  
Xuan Tang ◽  
...  

Background: Every year, nearly 170,000 people die from bladder cancer worldwide. A major problem after transurethral resection of bladder tumor is that 40–80% of the tumors recur. Ferroptosis is a type of regulatory necrosis mediated by iron-catalyzed, excessive oxidation of polyunsaturated fatty acids. Increasing the sensitivity of tumor cells to ferroptosis is a potential treatment option for cancer. Establishing a diagnostic and prognostic model based on ferroptosis-related genes may provide guidance for the precise treatment of bladder cancer.Methods: We downloaded mRNA data in Bladder Cancer from The Cancer Genome Atlas and analyzed differentially expressed genes based on and extract ferroptosis-related genes. We identified relevant pathways and annotate the functions of ferroptosis-related DEGs using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology functions. On the website of Search Tool for Retrieving Interacting Genes database (STRING), we downloaded the protein-protein interactions of DEGs, which were drawn by the Cytoscape software. Then the Cox regression analysis were performed so that the prognostic value of ferroptosis-related genes and survival time are combined to identify survival- and ferroptosis-related genes and establish a prognostic formula. Survival analysis and receiver operating characteristic curvevalidation were then performed. Risk curves and nomograms were generated for both groups to predict survival. Finally, RT-qPCR was applied to analyze gene expression.Results: Eight ferroptosis-related genes with prognostic value (ISCU, NFE2L2, MAFG, ZEB1, VDAC2, TXNIP, SCD, and JDP2) were identified. With clinical data, we established a prognostic model to provide promising diagnostic and prognostic information of bladder cancer based on the eight ferroptosis-related genes. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues.Conclusion: This study found that the ferroptosis-related genes is associated with bladder cancer, which may serve as new target for the treatment of bladder cancer.


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