Cargando…

Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be criticall...

Descripción completa

Detalles Bibliográficos
Autores principales: Deng, Yulin, Guo, Kai, Tang, Zhenfeng, Feng, Yuanfa, Cai, Shanghua, Ye, Jianheng, Xi, Yuanxue, Li, Jinchuang, Liu, Ren, Cai, Chao, Tan, Zeheng, Zhang, Yixun, Han, Zhaodong, Zeng, Guohua, Zhong, Weide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730408/
https://www.ncbi.nlm.nih.gov/pubmed/36505457
http://dx.doi.org/10.3389/fimmu.2022.1046790
_version_ 1784845663548211200
author Deng, Yulin
Guo, Kai
Tang, Zhenfeng
Feng, Yuanfa
Cai, Shanghua
Ye, Jianheng
Xi, Yuanxue
Li, Jinchuang
Liu, Ren
Cai, Chao
Tan, Zeheng
Zhang, Yixun
Han, Zhaodong
Zeng, Guohua
Zhong, Weide
author_facet Deng, Yulin
Guo, Kai
Tang, Zhenfeng
Feng, Yuanfa
Cai, Shanghua
Ye, Jianheng
Xi, Yuanxue
Li, Jinchuang
Liu, Ren
Cai, Chao
Tan, Zeheng
Zhang, Yixun
Han, Zhaodong
Zeng, Guohua
Zhong, Weide
author_sort Deng, Yulin
collection PubMed
description Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be critically associated with the differentiation and maturation of tumor-infiltrating lymphocytes (TILs), which work against tumor cells. In this study, we identified 10 TIL-related lncRNAs (AL590094.1, LINC02027, LINC00460, AC147651.1, AC026401.3, LINC00944, LINC01615, AP000439.2, AL162586.1, and AC084876.1) by Pearson correlation, univariate Cox regression, Lasso regression, and multivariate Cox regression based on The Cancer Genome Atlas (TCGA) database. A risk score model was established based on these lncRNAs. Next, a nomogram was constructed to predict the overall survival. By employing differentially expressed genes (DEGs) between groups with high and low risk scores, gene ontology (GO) enrichment analysis was performed to identify the major biological processes (BP) related to immune DEGs. We analyzed the mutation data of the groups and demonstrated that SETD2 and BAP1 had the highest mutation frequency in the high-risk group. The “CIBERSORT” R package was used to detect the abundance of TILs in the groups. The expression of lymphocyte markers was compared. We also determined the expression of two lncRNAs (AC084876.1 and AC026401.3) and their relationship with lymphocyte markers in the kidney tissue of ccRCC patients and showed that there was a positive correlation between AC084876.1 and FoxP3. Proliferation, migration, and invasion of AC084876.1-downregulated ccRCC cell lines were inhibited, and the expression of PD-L1 and TGF-β secretion decreased. To our knowledge, this is the first bioinformatics study to establish a prognostic model for ccRCC using TIL-related lncRNAs. These lncRNAs were associated with T-cell activities and may serve as biomarkers of disease prognosis.
format Online
Article
Text
id pubmed-9730408
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-97304082022-12-09 Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma Deng, Yulin Guo, Kai Tang, Zhenfeng Feng, Yuanfa Cai, Shanghua Ye, Jianheng Xi, Yuanxue Li, Jinchuang Liu, Ren Cai, Chao Tan, Zeheng Zhang, Yixun Han, Zhaodong Zeng, Guohua Zhong, Weide Front Immunol Immunology Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be critically associated with the differentiation and maturation of tumor-infiltrating lymphocytes (TILs), which work against tumor cells. In this study, we identified 10 TIL-related lncRNAs (AL590094.1, LINC02027, LINC00460, AC147651.1, AC026401.3, LINC00944, LINC01615, AP000439.2, AL162586.1, and AC084876.1) by Pearson correlation, univariate Cox regression, Lasso regression, and multivariate Cox regression based on The Cancer Genome Atlas (TCGA) database. A risk score model was established based on these lncRNAs. Next, a nomogram was constructed to predict the overall survival. By employing differentially expressed genes (DEGs) between groups with high and low risk scores, gene ontology (GO) enrichment analysis was performed to identify the major biological processes (BP) related to immune DEGs. We analyzed the mutation data of the groups and demonstrated that SETD2 and BAP1 had the highest mutation frequency in the high-risk group. The “CIBERSORT” R package was used to detect the abundance of TILs in the groups. The expression of lymphocyte markers was compared. We also determined the expression of two lncRNAs (AC084876.1 and AC026401.3) and their relationship with lymphocyte markers in the kidney tissue of ccRCC patients and showed that there was a positive correlation between AC084876.1 and FoxP3. Proliferation, migration, and invasion of AC084876.1-downregulated ccRCC cell lines were inhibited, and the expression of PD-L1 and TGF-β secretion decreased. To our knowledge, this is the first bioinformatics study to establish a prognostic model for ccRCC using TIL-related lncRNAs. These lncRNAs were associated with T-cell activities and may serve as biomarkers of disease prognosis. Frontiers Media S.A. 2022-11-24 /pmc/articles/PMC9730408/ /pubmed/36505457 http://dx.doi.org/10.3389/fimmu.2022.1046790 Text en Copyright © 2022 Deng, Guo, Tang, Feng, Cai, Ye, Xi, Li, Liu, Cai, Tan, Zhang, Han, Zeng and Zhong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Deng, Yulin
Guo, Kai
Tang, Zhenfeng
Feng, Yuanfa
Cai, Shanghua
Ye, Jianheng
Xi, Yuanxue
Li, Jinchuang
Liu, Ren
Cai, Chao
Tan, Zeheng
Zhang, Yixun
Han, Zhaodong
Zeng, Guohua
Zhong, Weide
Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma
title Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma
title_full Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma
title_fullStr Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma
title_full_unstemmed Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma
title_short Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma
title_sort identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding rna signature for prognosis of clear cell renal cell carcinoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730408/
https://www.ncbi.nlm.nih.gov/pubmed/36505457
http://dx.doi.org/10.3389/fimmu.2022.1046790
work_keys_str_mv AT dengyulin identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT guokai identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT tangzhenfeng identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT fengyuanfa identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT caishanghua identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT yejianheng identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT xiyuanxue identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT lijinchuang identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT liuren identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT caichao identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT tanzeheng identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT zhangyixun identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT hanzhaodong identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT zengguohua identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma
AT zhongweide identificationandexperimentalvalidationofatumorinfiltratinglymphocytesrelatedlongnoncodingrnasignatureforprognosisofclearcellrenalcellcarcinoma