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A Novel Autophagy-Related Long Non-Coding RNA Signature to Predict Prognosis and Therapeutic Response in Esophageal Squamous Cell Carcinoma

BACKGROUND: Considering the significance of autophagy and long non-coding RNAs (lncRNAs) in the biology of esophageal squamous cell carcinoma (ESCC), the present study aimed to identify a new autophagy-related lncRNA signature to forecast the clinical outcomes of ESCC patients and to guide individua...

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Autores principales: Shi, Xiaobo, Liu, Xiaoxiao, Pan, Shupei, Ke, Yue, Li, Yuxing, Guo, Wei, Wang, Yuchen, Ruan, Qinli, Zhang, Xiaozhi, Ma, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605829/
https://www.ncbi.nlm.nih.gov/pubmed/34815705
http://dx.doi.org/10.2147/IJGM.S333697
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author Shi, Xiaobo
Liu, Xiaoxiao
Pan, Shupei
Ke, Yue
Li, Yuxing
Guo, Wei
Wang, Yuchen
Ruan, Qinli
Zhang, Xiaozhi
Ma, Hongbing
author_facet Shi, Xiaobo
Liu, Xiaoxiao
Pan, Shupei
Ke, Yue
Li, Yuxing
Guo, Wei
Wang, Yuchen
Ruan, Qinli
Zhang, Xiaozhi
Ma, Hongbing
author_sort Shi, Xiaobo
collection PubMed
description BACKGROUND: Considering the significance of autophagy and long non-coding RNAs (lncRNAs) in the biology of esophageal squamous cell carcinoma (ESCC), the present study aimed to identify a new autophagy-related lncRNA signature to forecast the clinical outcomes of ESCC patients and to guide individualized treatment. METHODS: The expression profiles were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. We extracted autophagy-related genes from the Human Autophagy Database and identified autophagy-related lncRNAs through Spearman correlation analysis. Univariate, least absolute shrinkage and selection operator and multivariate Cox regression analyses were performed on GSE53625 to construct an autophagy-related lncRNAs prognostic signature. The model was subjected to bootstrap internal validation, and the expression levels of lncRNAs were verified by TCGA database. The potential molecular mechanism of the model was explored by gene set enrichment analysis (GSEA). Spearman correlation coefficient examined the correlation between risk score and ferroptosis-associated genes as well as the response to immunotherapy and chemotherapy. RESULTS: We identified and validated an autophagy-related lncRNAs prognostic signature in 179 patients with ESCC. The prognosis of patients in the low-risk group was significantly better than that in the high-risk group (p-value <0.001). The reliability of the model was verified by Brier score and ROC. GSEA results showed significant enrichment of cancer- and autophagy-related signaling pathways in the high-risk group and metabolism-related pathways in the low-risk group. Correlation analysis indicated that the model can effectively forecast the effect of immunotherapy and chemotherapy. About 35.41% (74/209) ferroptosis-related genes were significantly correlated with risk scores. CONCLUSION: In brief, we constructed a novel autophagy-related lncRNAs signature (LINC02024, LINC01711, LINC01419, LCAL1, FENDRR, ADAMTS9-AS1, AC025244.1, AC015908.6 and AC011997.1), which could improve the prediction of clinical outcomes and guide individualized treatment of ESCC patients.
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spelling pubmed-86058292021-11-22 A Novel Autophagy-Related Long Non-Coding RNA Signature to Predict Prognosis and Therapeutic Response in Esophageal Squamous Cell Carcinoma Shi, Xiaobo Liu, Xiaoxiao Pan, Shupei Ke, Yue Li, Yuxing Guo, Wei Wang, Yuchen Ruan, Qinli Zhang, Xiaozhi Ma, Hongbing Int J Gen Med Original Research BACKGROUND: Considering the significance of autophagy and long non-coding RNAs (lncRNAs) in the biology of esophageal squamous cell carcinoma (ESCC), the present study aimed to identify a new autophagy-related lncRNA signature to forecast the clinical outcomes of ESCC patients and to guide individualized treatment. METHODS: The expression profiles were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. We extracted autophagy-related genes from the Human Autophagy Database and identified autophagy-related lncRNAs through Spearman correlation analysis. Univariate, least absolute shrinkage and selection operator and multivariate Cox regression analyses were performed on GSE53625 to construct an autophagy-related lncRNAs prognostic signature. The model was subjected to bootstrap internal validation, and the expression levels of lncRNAs were verified by TCGA database. The potential molecular mechanism of the model was explored by gene set enrichment analysis (GSEA). Spearman correlation coefficient examined the correlation between risk score and ferroptosis-associated genes as well as the response to immunotherapy and chemotherapy. RESULTS: We identified and validated an autophagy-related lncRNAs prognostic signature in 179 patients with ESCC. The prognosis of patients in the low-risk group was significantly better than that in the high-risk group (p-value <0.001). The reliability of the model was verified by Brier score and ROC. GSEA results showed significant enrichment of cancer- and autophagy-related signaling pathways in the high-risk group and metabolism-related pathways in the low-risk group. Correlation analysis indicated that the model can effectively forecast the effect of immunotherapy and chemotherapy. About 35.41% (74/209) ferroptosis-related genes were significantly correlated with risk scores. CONCLUSION: In brief, we constructed a novel autophagy-related lncRNAs signature (LINC02024, LINC01711, LINC01419, LCAL1, FENDRR, ADAMTS9-AS1, AC025244.1, AC015908.6 and AC011997.1), which could improve the prediction of clinical outcomes and guide individualized treatment of ESCC patients. Dove 2021-11-16 /pmc/articles/PMC8605829/ /pubmed/34815705 http://dx.doi.org/10.2147/IJGM.S333697 Text en © 2021 Shi et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Shi, Xiaobo
Liu, Xiaoxiao
Pan, Shupei
Ke, Yue
Li, Yuxing
Guo, Wei
Wang, Yuchen
Ruan, Qinli
Zhang, Xiaozhi
Ma, Hongbing
A Novel Autophagy-Related Long Non-Coding RNA Signature to Predict Prognosis and Therapeutic Response in Esophageal Squamous Cell Carcinoma
title A Novel Autophagy-Related Long Non-Coding RNA Signature to Predict Prognosis and Therapeutic Response in Esophageal Squamous Cell Carcinoma
title_full A Novel Autophagy-Related Long Non-Coding RNA Signature to Predict Prognosis and Therapeutic Response in Esophageal Squamous Cell Carcinoma
title_fullStr A Novel Autophagy-Related Long Non-Coding RNA Signature to Predict Prognosis and Therapeutic Response in Esophageal Squamous Cell Carcinoma
title_full_unstemmed A Novel Autophagy-Related Long Non-Coding RNA Signature to Predict Prognosis and Therapeutic Response in Esophageal Squamous Cell Carcinoma
title_short A Novel Autophagy-Related Long Non-Coding RNA Signature to Predict Prognosis and Therapeutic Response in Esophageal Squamous Cell Carcinoma
title_sort novel autophagy-related long non-coding rna signature to predict prognosis and therapeutic response in esophageal squamous cell carcinoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605829/
https://www.ncbi.nlm.nih.gov/pubmed/34815705
http://dx.doi.org/10.2147/IJGM.S333697
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