Integrated analysis on the N6‐methyladenosine‐related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinoma

Abstract Background Patients with advanced clear cell renal cell carcinoma (ccRCC) have a poor prognosis and lack effective prognostic biomarkers. N6‐methyladenosine‐related lncRNAs (m6A‐related long noncoding RNAs [lncRNAs]) have been confirmed to be associated with the development of multiple tumo...

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Main Authors: Yuqin Qiu, Xiaogang Wang, Zhenjia Fan, Shanhui Zhan, Xin Jiang, Jinchang Huang
Format: Article
Language:English
Published: Wiley 2021-12-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.513
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author Yuqin Qiu
Xiaogang Wang
Zhenjia Fan
Shanhui Zhan
Xin Jiang
Jinchang Huang
author_facet Yuqin Qiu
Xiaogang Wang
Zhenjia Fan
Shanhui Zhan
Xin Jiang
Jinchang Huang
author_sort Yuqin Qiu
collection DOAJ
description Abstract Background Patients with advanced clear cell renal cell carcinoma (ccRCC) have a poor prognosis and lack effective prognostic biomarkers. N6‐methyladenosine‐related lncRNAs (m6A‐related long noncoding RNAs [lncRNAs]) have been confirmed to be associated with the development of multiple tumors, but its role in ccRCC is not clear. Methods Gene expression data and clinical information of ccRCC patients were extracted from The Cancer Genome Atlas Database. The prognostic m6A‐related lncRNAs were obtained by Pearson's correlation analysis and univariate Cox regression analysis. Afterward, the cluster classification and its correlation with prognosis, clinical characteristics, and immunity were analyzed. LASSO regression was used to establish the prognostic risk model. The predictive performance of the prognostic model was evaluated and validated by survival analysis and receiver operating characteristic curve analysis, et al. The expression of immune checkpoints and immune cell infiltration in patients with different risks were systematically analyzed. Results A total of 27 prognostic m6A‐related lncRNAs were identified. These m6A‐related lncRNAs were differentially expressed between tumor and normal tissues. Among them, 24 high‐risk m6A‐related lncRNAs were overexpressed in Cluster 2 and correlated with poor prognosis, low stromal score, high expression of immune checkpoints, and immunosuppressive cells infiltration. Based upon, a prognostic risk model composed of seven m6A‐related lncRNAs was constructed. After a series of analyses, it was proved that this model had good sensitivity and specificity, and could predict the prognosis of patients with different clinical stratification. The expression of PD‐1, PD‐L1, CTLA‐4, LAG‐3, TIM‐3, and TIGIT were significantly increased in the high‐risk patients, and there was a correlation between the risk score and immune cell infiltration. Conclusions The seven m6A‐related lncRNAs prognostic risk signature showed reliable prognostic predictive power for ccRCC and was associated with the expression of immune checkpoints and immune cell infiltration. This seven m6A‐related lncRNAs signature will be helpful in managing ccRCC and guiding individualized immunotherapy.
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spelling doaj.art-794f637b6b61404eb318fba3c0d267b62022-12-21T19:22:39ZengWileyImmunity, Inflammation and Disease2050-45272021-12-01941596161210.1002/iid3.513Integrated analysis on the N6‐methyladenosine‐related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinomaYuqin Qiu0Xiaogang Wang1Zhenjia Fan2Shanhui Zhan3Xin Jiang4Jinchang Huang5Third Affiliated Hospital Beijing University of Chinese Medicine Beijing ChinaDepartment of Emergency Medicine, Beijing Haidian Hospital Haidian Section of Peking University Third Hospital Beijing ChinaThird Affiliated Hospital Beijing University of Chinese Medicine Beijing ChinaThird Affiliated Hospital Beijing University of Chinese Medicine Beijing ChinaThird Affiliated Hospital Beijing University of Chinese Medicine Beijing ChinaThird Affiliated Hospital Beijing University of Chinese Medicine Beijing ChinaAbstract Background Patients with advanced clear cell renal cell carcinoma (ccRCC) have a poor prognosis and lack effective prognostic biomarkers. N6‐methyladenosine‐related lncRNAs (m6A‐related long noncoding RNAs [lncRNAs]) have been confirmed to be associated with the development of multiple tumors, but its role in ccRCC is not clear. Methods Gene expression data and clinical information of ccRCC patients were extracted from The Cancer Genome Atlas Database. The prognostic m6A‐related lncRNAs were obtained by Pearson's correlation analysis and univariate Cox regression analysis. Afterward, the cluster classification and its correlation with prognosis, clinical characteristics, and immunity were analyzed. LASSO regression was used to establish the prognostic risk model. The predictive performance of the prognostic model was evaluated and validated by survival analysis and receiver operating characteristic curve analysis, et al. The expression of immune checkpoints and immune cell infiltration in patients with different risks were systematically analyzed. Results A total of 27 prognostic m6A‐related lncRNAs were identified. These m6A‐related lncRNAs were differentially expressed between tumor and normal tissues. Among them, 24 high‐risk m6A‐related lncRNAs were overexpressed in Cluster 2 and correlated with poor prognosis, low stromal score, high expression of immune checkpoints, and immunosuppressive cells infiltration. Based upon, a prognostic risk model composed of seven m6A‐related lncRNAs was constructed. After a series of analyses, it was proved that this model had good sensitivity and specificity, and could predict the prognosis of patients with different clinical stratification. The expression of PD‐1, PD‐L1, CTLA‐4, LAG‐3, TIM‐3, and TIGIT were significantly increased in the high‐risk patients, and there was a correlation between the risk score and immune cell infiltration. Conclusions The seven m6A‐related lncRNAs prognostic risk signature showed reliable prognostic predictive power for ccRCC and was associated with the expression of immune checkpoints and immune cell infiltration. This seven m6A‐related lncRNAs signature will be helpful in managing ccRCC and guiding individualized immunotherapy.https://doi.org/10.1002/iid3.513clear cell renal cell carcinomaimmune cell infiltrationimmune checkpointlong noncoding RNAN6‐methyladenosineprognosis
spellingShingle Yuqin Qiu
Xiaogang Wang
Zhenjia Fan
Shanhui Zhan
Xin Jiang
Jinchang Huang
Integrated analysis on the N6‐methyladenosine‐related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinoma
Immunity, Inflammation and Disease
clear cell renal cell carcinoma
immune cell infiltration
immune checkpoint
long noncoding RNA
N6‐methyladenosine
prognosis
title Integrated analysis on the N6‐methyladenosine‐related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinoma
title_full Integrated analysis on the N6‐methyladenosine‐related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinoma
title_fullStr Integrated analysis on the N6‐methyladenosine‐related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinoma
title_full_unstemmed Integrated analysis on the N6‐methyladenosine‐related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinoma
title_short Integrated analysis on the N6‐methyladenosine‐related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinoma
title_sort integrated analysis on the n6 methyladenosine related long noncoding rnas prognostic signature immune checkpoints and immune cell infiltration in clear cell renal cell carcinoma
topic clear cell renal cell carcinoma
immune cell infiltration
immune checkpoint
long noncoding RNA
N6‐methyladenosine
prognosis
url https://doi.org/10.1002/iid3.513
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