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The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress
Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail. Methods: First, the RNAseq data and clinical data of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551162/ https://www.ncbi.nlm.nih.gov/pubmed/37808187 http://dx.doi.org/10.3389/fphar.2023.1234181 |
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author | Lv, Xuefeng Jia, Yanyan Li, Jinpeng Deng, Shu Yuan, Enwu |
author_facet | Lv, Xuefeng Jia, Yanyan Li, Jinpeng Deng, Shu Yuan, Enwu |
author_sort | Lv, Xuefeng |
collection | PubMed |
description | Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail. Methods: First, the RNAseq data and clinical data of CC patients were collected from The Cancer Genome Atlas (TCGA) database, along with the immune genes from the Import database. We used univariate cox and least absolute shrinkage and selection operator (lasso) to obtain IRLs for prediction after screening the variables. According to the expression levels and risk coefficients of IRLs, the riskscore were calculated. We analyzed the relationship between the model and oxidative stress. We stratified the risk model into two as the high and low-risk groups. We also evaluated the survival differences, immune cell differences, immunotherapeutic response differences, and drug sensitivity differences between the risk groups. Finally, the genes in the model were experimentally validated. Results: Based on the above analyses, we further selected four IRLs (TFAP2A.AS1, AP000911.1, AL133215.2, and LINC02078) to construct the risk model. The model was associated with oxidative-stress-related genes, especially SOD2 and OGG1. Patients in the high-risk group had a lower overall survival than those in the low-risk group. Riskscore was positively correlated with resting mast cells, neutrophils, and CD8+ T-cells. Patients in the low-risk group showed a greater sensitivity to immunosuppression therapy. In addition, we found that patients with the PIK3CA mutation were more sensitive to chemotherapeutic agents such as dasatinib, afatinib, dinaciclib and pelitinib. The function of AL133215.2 was verified, which was consistent with previous findings, and AL133215.2 exerted a pro-tumorigenic effect. We also found that AL133215.2 was closely associated with oxidative-stress-related pathways. Discussion: The results suggested that risk modeling might be useful for prognosticating patients with CC and opening up new routes for immunotherapy. |
format | Online Article Text |
id | pubmed-10551162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105511622023-10-06 The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress Lv, Xuefeng Jia, Yanyan Li, Jinpeng Deng, Shu Yuan, Enwu Front Pharmacol Pharmacology Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail. Methods: First, the RNAseq data and clinical data of CC patients were collected from The Cancer Genome Atlas (TCGA) database, along with the immune genes from the Import database. We used univariate cox and least absolute shrinkage and selection operator (lasso) to obtain IRLs for prediction after screening the variables. According to the expression levels and risk coefficients of IRLs, the riskscore were calculated. We analyzed the relationship between the model and oxidative stress. We stratified the risk model into two as the high and low-risk groups. We also evaluated the survival differences, immune cell differences, immunotherapeutic response differences, and drug sensitivity differences between the risk groups. Finally, the genes in the model were experimentally validated. Results: Based on the above analyses, we further selected four IRLs (TFAP2A.AS1, AP000911.1, AL133215.2, and LINC02078) to construct the risk model. The model was associated with oxidative-stress-related genes, especially SOD2 and OGG1. Patients in the high-risk group had a lower overall survival than those in the low-risk group. Riskscore was positively correlated with resting mast cells, neutrophils, and CD8+ T-cells. Patients in the low-risk group showed a greater sensitivity to immunosuppression therapy. In addition, we found that patients with the PIK3CA mutation were more sensitive to chemotherapeutic agents such as dasatinib, afatinib, dinaciclib and pelitinib. The function of AL133215.2 was verified, which was consistent with previous findings, and AL133215.2 exerted a pro-tumorigenic effect. We also found that AL133215.2 was closely associated with oxidative-stress-related pathways. Discussion: The results suggested that risk modeling might be useful for prognosticating patients with CC and opening up new routes for immunotherapy. Frontiers Media S.A. 2023-09-21 /pmc/articles/PMC10551162/ /pubmed/37808187 http://dx.doi.org/10.3389/fphar.2023.1234181 Text en Copyright © 2023 Lv, Jia, Li, Deng and Yuan. 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 | Pharmacology Lv, Xuefeng Jia, Yanyan Li, Jinpeng Deng, Shu Yuan, Enwu The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress |
title | The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress |
title_full | The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress |
title_fullStr | The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress |
title_full_unstemmed | The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress |
title_short | The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress |
title_sort | construction of a prognostic model of cervical cancer based on four immune-related lncrnas and an exploration of the correlations between the model and oxidative stress |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551162/ https://www.ncbi.nlm.nih.gov/pubmed/37808187 http://dx.doi.org/10.3389/fphar.2023.1234181 |
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