A Novel Immune-Related lncRNA-Based Model for Survival Prediction in Clear Cell Renal Cell Carcinoma

Background. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer whose incidence and mortality rate are increasing. Identifying immune-related lncRNAs and constructing a model would probably provide new insights into biomarkers and immunotherapy for ccRCC and aid in th...

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Main Authors: Zedan Zhang, Yanlin Tang, Yanjun Liu, Hongkai Zhuang, Enyu Lin, Lu Xie, Xiaoqiang Feng, Kaiwen Tian, Jiayi Zeng, Jiumin Liu, Yuming Yu
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/9921466
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author Zedan Zhang
Yanlin Tang
Yanjun Liu
Hongkai Zhuang
Enyu Lin
Lu Xie
Xiaoqiang Feng
Kaiwen Tian
Jiayi Zeng
Jiumin Liu
Yuming Yu
author_facet Zedan Zhang
Yanlin Tang
Yanjun Liu
Hongkai Zhuang
Enyu Lin
Lu Xie
Xiaoqiang Feng
Kaiwen Tian
Jiayi Zeng
Jiumin Liu
Yuming Yu
author_sort Zedan Zhang
collection DOAJ
description Background. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer whose incidence and mortality rate are increasing. Identifying immune-related lncRNAs and constructing a model would probably provide new insights into biomarkers and immunotherapy for ccRCC and aid in the prognosis prediction. Methods. The transcription profile and clinical information were obtained from The Cancer Genome Atlas (TCGA). Immune-related gene sets and transcription factor genes were downloaded from GSEA website and Cistrome database, respectively. Tumor samples were divided into the training set and the testing set. Immune-related differentially expressed lncRNAs (IDElncRNAs) were identified from the whole set. Univariate Cox regression, LASSO, and stepwise multivariate Cox regression were performed to screen out ideal prognostic IDElncRNAs (PIDElncRNAs) from the training set and develop a multi-lncRNA signature. Results. Consequently, AC012236.1, AC078778.1, AC078950.1, AC087318.1, and AC092535.4 were screened to be significantly related to the prognosis of ccRCC patients, which were used to establish the five-lncRNA signature. Its wide diagnostic capacity was revealed in different subgroups of clinical parameters. Then AJCC-stage, Fuhrman-grade, pharmaceutical, age, and risk score regarded as independent prognostic factors were integrated to construct a nomogram, whose good performance in predicting 3-, 5-, and 7-year overall survival of ccRCC patients was revealed by time-dependent ROC curves and verified by the testing sets and ICGC dataset. The calibration plots showed great agreement of the nomogram between predicted and observed outcomes. Functional enrichment analysis showed the signature and each lncRNA were mainly enriched in pathways associated with regulation of immune response. Several kinds of tumor-infiltrating immune cells like regulatory T cells, T follicular helper cells, CD8+ T cells, resting mast cells, and naïve B cells were significantly correlated with the signature. Conclusion. Therefore, we constructed a five-lncRNA model integrating clinical parameters to help predict the prognosis of ccRCC patients. The five immune-related lncRNAs could potentially be therapeutic targets for immunotherapy in ccRCC in the future.
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issn 2314-8861
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publishDate 2021-01-01
publisher Wiley
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series Journal of Immunology Research
spelling doaj-art-595a23443e0145a5906309ef8de800932025-02-03T05:44:08ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/99214669921466A Novel Immune-Related lncRNA-Based Model for Survival Prediction in Clear Cell Renal Cell CarcinomaZedan Zhang0Yanlin Tang1Yanjun Liu2Hongkai Zhuang3Enyu Lin4Lu Xie5Xiaoqiang Feng6Kaiwen Tian7Jiayi Zeng8Jiumin Liu9Yuming Yu10Department of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou, ChinaShantou University Medical College, Shantou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaCenter of Stem Cell and Regenerative Medicine, Gaozhou People’s Hospital, Maoming, Guangdong, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaBackground. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer whose incidence and mortality rate are increasing. Identifying immune-related lncRNAs and constructing a model would probably provide new insights into biomarkers and immunotherapy for ccRCC and aid in the prognosis prediction. Methods. The transcription profile and clinical information were obtained from The Cancer Genome Atlas (TCGA). Immune-related gene sets and transcription factor genes were downloaded from GSEA website and Cistrome database, respectively. Tumor samples were divided into the training set and the testing set. Immune-related differentially expressed lncRNAs (IDElncRNAs) were identified from the whole set. Univariate Cox regression, LASSO, and stepwise multivariate Cox regression were performed to screen out ideal prognostic IDElncRNAs (PIDElncRNAs) from the training set and develop a multi-lncRNA signature. Results. Consequently, AC012236.1, AC078778.1, AC078950.1, AC087318.1, and AC092535.4 were screened to be significantly related to the prognosis of ccRCC patients, which were used to establish the five-lncRNA signature. Its wide diagnostic capacity was revealed in different subgroups of clinical parameters. Then AJCC-stage, Fuhrman-grade, pharmaceutical, age, and risk score regarded as independent prognostic factors were integrated to construct a nomogram, whose good performance in predicting 3-, 5-, and 7-year overall survival of ccRCC patients was revealed by time-dependent ROC curves and verified by the testing sets and ICGC dataset. The calibration plots showed great agreement of the nomogram between predicted and observed outcomes. Functional enrichment analysis showed the signature and each lncRNA were mainly enriched in pathways associated with regulation of immune response. Several kinds of tumor-infiltrating immune cells like regulatory T cells, T follicular helper cells, CD8+ T cells, resting mast cells, and naïve B cells were significantly correlated with the signature. Conclusion. Therefore, we constructed a five-lncRNA model integrating clinical parameters to help predict the prognosis of ccRCC patients. The five immune-related lncRNAs could potentially be therapeutic targets for immunotherapy in ccRCC in the future.http://dx.doi.org/10.1155/2021/9921466
spellingShingle Zedan Zhang
Yanlin Tang
Yanjun Liu
Hongkai Zhuang
Enyu Lin
Lu Xie
Xiaoqiang Feng
Kaiwen Tian
Jiayi Zeng
Jiumin Liu
Yuming Yu
A Novel Immune-Related lncRNA-Based Model for Survival Prediction in Clear Cell Renal Cell Carcinoma
Journal of Immunology Research
title A Novel Immune-Related lncRNA-Based Model for Survival Prediction in Clear Cell Renal Cell Carcinoma
title_full A Novel Immune-Related lncRNA-Based Model for Survival Prediction in Clear Cell Renal Cell Carcinoma
title_fullStr A Novel Immune-Related lncRNA-Based Model for Survival Prediction in Clear Cell Renal Cell Carcinoma
title_full_unstemmed A Novel Immune-Related lncRNA-Based Model for Survival Prediction in Clear Cell Renal Cell Carcinoma
title_short A Novel Immune-Related lncRNA-Based Model for Survival Prediction in Clear Cell Renal Cell Carcinoma
title_sort novel immune related lncrna based model for survival prediction in clear cell renal cell carcinoma
url http://dx.doi.org/10.1155/2021/9921466
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