Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer

AbstractObjective This study aims to evaluate the prognostic value of m6A-associated long noncoding RNAs (lncRNAs) and their interaction with tumour microenvironment in thyroid cancer (THCA).Methods The clinical and gene expression data of tumours from 502 patients with THCA and 58 adjacent normal t...

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Main Authors: Yongcheng Su, Beibei Xu, Jiangquan Li, Qianwen Shen, Ziyu Lei, Miaomiao Ma, Fuxing Zhang, Tianhui Hu
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Annals of Medicine
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2023.2192049
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author Yongcheng Su
Beibei Xu
Jiangquan Li
Qianwen Shen
Ziyu Lei
Miaomiao Ma
Fuxing Zhang
Tianhui Hu
author_facet Yongcheng Su
Beibei Xu
Jiangquan Li
Qianwen Shen
Ziyu Lei
Miaomiao Ma
Fuxing Zhang
Tianhui Hu
author_sort Yongcheng Su
collection DOAJ
description AbstractObjective This study aims to evaluate the prognostic value of m6A-associated long noncoding RNAs (lncRNAs) and their interaction with tumour microenvironment in thyroid cancer (THCA).Methods The clinical and gene expression data of tumours from 502 patients with THCA and 58 adjacent normal tissues were retrieved from The Cancer Genome Atlas (TCGA)–THCA dataset. The Pearson test was utilized to identify potential m6A-associated lncRNAs (p < 0.001 and Pearson correlation coefficient > 0.4). Quantitative real-time polymerase chain reaction was performed to verify the expression levels of lncRNAs in tissues. MTT, EdU, colony formation and wound-healing assays were performed to determine the functions of m6A-associated lncRNAs in THCA cell proliferation and metastasis.Results M6A-associated lncRNAs were identified in three cluster groups. A significant survival difference was found among them, with cluster 1 patients showing worse survival. Moreover, lower immune and estimate scores were correlated to poorer prognosis, and CD8+ T cell and memory CD4+ T cell levels were increased in cluster 1. Cluster 2, with better overall survival, had high expression of PD-L1 and CTLA-4. Eleven of the m6A-associated lncRNAs were screened to establish the risk model, including AC007365.1, AC008555.1, AC040160.1, AC064807.1, AC126773.4, AL023583.1, AL512306.2, EIF2AK3-DT, LINC00667, LYPLAL1-DT and MIR181A2HG. Based on the median risk score, THCA patients were stratified into low-risk and high-risk groups. Overall survival analysis showed a dramatic difference between the two groups. qRCR was performed to verify the expression levels of lncRNA (LYPLAL1-DT, EIF2AK3-DT and MIR181A2HG) in THCA and adjacent normal tissues. Furthermore, functional experiments showed that knockdown of MIR181A2HG obviously inhibited the proliferation and migration of papillary thyroid cancer (PTC) cells in vitro, whereas LYPLAL1-DT overexpression promoted PTC cell proliferation and migration.Conclusions Eleven of the m6A-associated lncRNAs were identified as a risk model to predict clinical outcomes and provide a novel and efficient immunotherapeutic strategy for THCA patients.Key messagesm6A-associated lncRNAs can be used to predict the clinical outcomes of thyroid cancer patients.An m6A-associated lncRNAs risk model, which can accurately evaluate the immune status and risk stratification in individual thyroid cancer patients, was established.Knockdown/overexpression of representative lncRNAs in the risk model significantly affected the proliferation and migration of papillary thyroid cancer cells.
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spelling doaj.art-a6c1be496dd44af999ea458b8bcf7e352024-01-16T19:13:20ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602023-12-015511298131610.1080/07853890.2023.2192049Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancerYongcheng Su0Beibei Xu1Jiangquan Li2Qianwen Shen3Ziyu Lei4Miaomiao Ma5Fuxing Zhang6Tianhui Hu7Department of General Surgery, The First Hospital affiliated to Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of General Surgery, The First Hospital affiliated to Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaCancer Research Center, Xiamen University School of Medicine, Xiamen, ChinaCancer Research Center, Xiamen University School of Medicine, Xiamen, ChinaCancer Research Center, Xiamen University School of Medicine, Xiamen, ChinaCancer Research Center, Xiamen University School of Medicine, Xiamen, ChinaDepartment of General Surgery, The First Hospital affiliated to Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of General Surgery, The First Hospital affiliated to Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaAbstractObjective This study aims to evaluate the prognostic value of m6A-associated long noncoding RNAs (lncRNAs) and their interaction with tumour microenvironment in thyroid cancer (THCA).Methods The clinical and gene expression data of tumours from 502 patients with THCA and 58 adjacent normal tissues were retrieved from The Cancer Genome Atlas (TCGA)–THCA dataset. The Pearson test was utilized to identify potential m6A-associated lncRNAs (p < 0.001 and Pearson correlation coefficient > 0.4). Quantitative real-time polymerase chain reaction was performed to verify the expression levels of lncRNAs in tissues. MTT, EdU, colony formation and wound-healing assays were performed to determine the functions of m6A-associated lncRNAs in THCA cell proliferation and metastasis.Results M6A-associated lncRNAs were identified in three cluster groups. A significant survival difference was found among them, with cluster 1 patients showing worse survival. Moreover, lower immune and estimate scores were correlated to poorer prognosis, and CD8+ T cell and memory CD4+ T cell levels were increased in cluster 1. Cluster 2, with better overall survival, had high expression of PD-L1 and CTLA-4. Eleven of the m6A-associated lncRNAs were screened to establish the risk model, including AC007365.1, AC008555.1, AC040160.1, AC064807.1, AC126773.4, AL023583.1, AL512306.2, EIF2AK3-DT, LINC00667, LYPLAL1-DT and MIR181A2HG. Based on the median risk score, THCA patients were stratified into low-risk and high-risk groups. Overall survival analysis showed a dramatic difference between the two groups. qRCR was performed to verify the expression levels of lncRNA (LYPLAL1-DT, EIF2AK3-DT and MIR181A2HG) in THCA and adjacent normal tissues. Furthermore, functional experiments showed that knockdown of MIR181A2HG obviously inhibited the proliferation and migration of papillary thyroid cancer (PTC) cells in vitro, whereas LYPLAL1-DT overexpression promoted PTC cell proliferation and migration.Conclusions Eleven of the m6A-associated lncRNAs were identified as a risk model to predict clinical outcomes and provide a novel and efficient immunotherapeutic strategy for THCA patients.Key messagesm6A-associated lncRNAs can be used to predict the clinical outcomes of thyroid cancer patients.An m6A-associated lncRNAs risk model, which can accurately evaluate the immune status and risk stratification in individual thyroid cancer patients, was established.Knockdown/overexpression of representative lncRNAs in the risk model significantly affected the proliferation and migration of papillary thyroid cancer cells.https://www.tandfonline.com/doi/10.1080/07853890.2023.2192049m6Athyroid cancerimmunotherapylncRNA
spellingShingle Yongcheng Su
Beibei Xu
Jiangquan Li
Qianwen Shen
Ziyu Lei
Miaomiao Ma
Fuxing Zhang
Tianhui Hu
Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer
Annals of Medicine
m6A
thyroid cancer
immunotherapy
lncRNA
title Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer
title_full Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer
title_fullStr Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer
title_full_unstemmed Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer
title_short Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer
title_sort identification of m6a associated lncrnas as predict factors for the immune infiltration and prognosis of thyroid cancer
topic m6A
thyroid cancer
immunotherapy
lncRNA
url https://www.tandfonline.com/doi/10.1080/07853890.2023.2192049
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