A novel molecular subtypes and risk model based on inflammatory response-related lncrnas for bladder cancer

Abstract Background Inflammation and long noncoding RNAs (lncRNAs) are gradually becoming important in the development of bladder cancer (BC). Nevertheless, the potential of inflammatory response-related lncRNAs (IRRlncRNAs) as a prognostic signature remains unexplored in BC. Methods The Cancer Geno...

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Main Authors: Fucai Tang, Jiahao Zhang, Zechao Lu, Haiqin Liao, Chuxian Hu, Yuexue Mai, Yongchang Lai, Zeguang Lu, Zhicheng Tang, Zhibiao Li, Zhaohui He
Format: Article
Language:English
Published: BMC 2022-08-01
Series:Hereditas
Subjects:
Online Access:https://doi.org/10.1186/s41065-022-00245-w
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author Fucai Tang
Jiahao Zhang
Zechao Lu
Haiqin Liao
Chuxian Hu
Yuexue Mai
Yongchang Lai
Zeguang Lu
Zhicheng Tang
Zhibiao Li
Zhaohui He
author_facet Fucai Tang
Jiahao Zhang
Zechao Lu
Haiqin Liao
Chuxian Hu
Yuexue Mai
Yongchang Lai
Zeguang Lu
Zhicheng Tang
Zhibiao Li
Zhaohui He
author_sort Fucai Tang
collection DOAJ
description Abstract Background Inflammation and long noncoding RNAs (lncRNAs) are gradually becoming important in the development of bladder cancer (BC). Nevertheless, the potential of inflammatory response-related lncRNAs (IRRlncRNAs) as a prognostic signature remains unexplored in BC. Methods The Cancer Genome Atlas (TCGA) provided RNA expression profiles and clinical information of BC samples, and GSEA Molecular Signatures database provided 1171 inflammation-related genes. IRRlncRNAs were identified using Pearson correlation analysis. After that, consensus clustering was performed to form molecular subtypes. After performing least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, a risk model constructed based on the prognostic IRRlncRNAs was validated in an independent cohort. Kaplan–Meier (KM) analysis, univariate and multivariate Cox regression, clinical stratification analysis, and time-dependent receiver operating characteristic (ROC) curves were utilized to assess clinical effectiveness and accuracy of the risk model. In clusters and risk model, functional enrichment was investigated using GSEA and GSVA, and immune cell infiltration analysis was demonstrated by ESTIMATE and CIBERSORT analysis. Results A total of 174 prognostic IRRlncRNAs were confirmed, and 406 samples were divided into 2 clusters, with cluster 2 having a significantly inferior prognosis. Moreover, cluster 2 exhibited a higher ESTIMATE score, immune infiltration, and PD-L1 expression, with close relationships with the inflammatory response. Further, 12 IRRlncRNAs were identified and applied to construct the risk model and divide BC samples into low-risk and high-risk groups successfully. KM, ROC, and clinical stratification analysis demonstrated that the risk model performed well in predicting prognosis. The risk score was identified as an independently significant indicator, enriched in immune, cell cycle, and apoptosis-related pathways, and correlated with 9 immune cells. Conclusion We developed an inflammatory response-related subtypes and steady prognostic risk model based on 12 IRRlncRNAs, which was valuable for individual prognostic prediction and stratification and outfitted new insight into inflammatory response in BC.
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spelling doaj.art-1550f6bc630541fe9ec43761cec26e952022-12-22T01:35:41ZengBMCHereditas1601-52232022-08-01159111610.1186/s41065-022-00245-wA novel molecular subtypes and risk model based on inflammatory response-related lncrnas for bladder cancerFucai Tang0Jiahao Zhang1Zechao Lu2Haiqin Liao3Chuxian Hu4Yuexue Mai5Yongchang Lai6Zeguang Lu7Zhicheng Tang8Zhibiao Li9Zhaohui He10Department of Urology, The Eighth Affiliated Hospital, Sun Yat-sen UniversityThe Sixth Clinical College of Guangzhou Medical UniversityDepartment of Urology, The Eighth Affiliated Hospital, Sun Yat-sen UniversityThe Second Clinical College of Guangzhou Medical UniversityThe Sixth Clinical College of Guangzhou Medical UniversityThe Sixth Clinical College of Guangzhou Medical UniversityDepartment of Urology, The Eighth Affiliated Hospital, Sun Yat-sen UniversityThe Second Clinical College of Guangzhou Medical UniversityThe Third Clinical College of Guangzhou Medical UniversityDepartment of Urology, The Eighth Affiliated Hospital, Sun Yat-sen UniversityDepartment of Urology, The Eighth Affiliated Hospital, Sun Yat-sen UniversityAbstract Background Inflammation and long noncoding RNAs (lncRNAs) are gradually becoming important in the development of bladder cancer (BC). Nevertheless, the potential of inflammatory response-related lncRNAs (IRRlncRNAs) as a prognostic signature remains unexplored in BC. Methods The Cancer Genome Atlas (TCGA) provided RNA expression profiles and clinical information of BC samples, and GSEA Molecular Signatures database provided 1171 inflammation-related genes. IRRlncRNAs were identified using Pearson correlation analysis. After that, consensus clustering was performed to form molecular subtypes. After performing least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, a risk model constructed based on the prognostic IRRlncRNAs was validated in an independent cohort. Kaplan–Meier (KM) analysis, univariate and multivariate Cox regression, clinical stratification analysis, and time-dependent receiver operating characteristic (ROC) curves were utilized to assess clinical effectiveness and accuracy of the risk model. In clusters and risk model, functional enrichment was investigated using GSEA and GSVA, and immune cell infiltration analysis was demonstrated by ESTIMATE and CIBERSORT analysis. Results A total of 174 prognostic IRRlncRNAs were confirmed, and 406 samples were divided into 2 clusters, with cluster 2 having a significantly inferior prognosis. Moreover, cluster 2 exhibited a higher ESTIMATE score, immune infiltration, and PD-L1 expression, with close relationships with the inflammatory response. Further, 12 IRRlncRNAs were identified and applied to construct the risk model and divide BC samples into low-risk and high-risk groups successfully. KM, ROC, and clinical stratification analysis demonstrated that the risk model performed well in predicting prognosis. The risk score was identified as an independently significant indicator, enriched in immune, cell cycle, and apoptosis-related pathways, and correlated with 9 immune cells. Conclusion We developed an inflammatory response-related subtypes and steady prognostic risk model based on 12 IRRlncRNAs, which was valuable for individual prognostic prediction and stratification and outfitted new insight into inflammatory response in BC.https://doi.org/10.1186/s41065-022-00245-wBladder cancerinflammatorylong noncoding RNATCGAprognosis
spellingShingle Fucai Tang
Jiahao Zhang
Zechao Lu
Haiqin Liao
Chuxian Hu
Yuexue Mai
Yongchang Lai
Zeguang Lu
Zhicheng Tang
Zhibiao Li
Zhaohui He
A novel molecular subtypes and risk model based on inflammatory response-related lncrnas for bladder cancer
Hereditas
Bladder cancer
inflammatory
long noncoding RNA
TCGA
prognosis
title A novel molecular subtypes and risk model based on inflammatory response-related lncrnas for bladder cancer
title_full A novel molecular subtypes and risk model based on inflammatory response-related lncrnas for bladder cancer
title_fullStr A novel molecular subtypes and risk model based on inflammatory response-related lncrnas for bladder cancer
title_full_unstemmed A novel molecular subtypes and risk model based on inflammatory response-related lncrnas for bladder cancer
title_short A novel molecular subtypes and risk model based on inflammatory response-related lncrnas for bladder cancer
title_sort novel molecular subtypes and risk model based on inflammatory response related lncrnas for bladder cancer
topic Bladder cancer
inflammatory
long noncoding RNA
TCGA
prognosis
url https://doi.org/10.1186/s41065-022-00245-w
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