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Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms

Background: Colon cancer, a prevalent and deadly malignancy worldwide, ranks as the third leading cause of cancer-related mortality. Disulfidptosis stress triggers a unique form of programmed cell death known as disulfidoptosis, characterized by excessive intracellular cystine accumulation. This stu...

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Autores principales: Chi, Hao, Huang, Jinbang, Yan, Yang, Jiang, Chenglu, Zhang, Shengke, Chen, Haiqing, Jiang, Lai, Zhang, Jieying, Zhang, Qinghong, Yang, Guanhu, Tian, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617599/
https://www.ncbi.nlm.nih.gov/pubmed/37916187
http://dx.doi.org/10.3389/fmolb.2023.1254232
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author Chi, Hao
Huang, Jinbang
Yan, Yang
Jiang, Chenglu
Zhang, Shengke
Chen, Haiqing
Jiang, Lai
Zhang, Jieying
Zhang, Qinghong
Yang, Guanhu
Tian, Gang
author_facet Chi, Hao
Huang, Jinbang
Yan, Yang
Jiang, Chenglu
Zhang, Shengke
Chen, Haiqing
Jiang, Lai
Zhang, Jieying
Zhang, Qinghong
Yang, Guanhu
Tian, Gang
author_sort Chi, Hao
collection PubMed
description Background: Colon cancer, a prevalent and deadly malignancy worldwide, ranks as the third leading cause of cancer-related mortality. Disulfidptosis stress triggers a unique form of programmed cell death known as disulfidoptosis, characterized by excessive intracellular cystine accumulation. This study aimed to establish reliable bioindicators based on long non-coding RNAs (LncRNAs) associated with disulfidptosis-induced cell death, providing novel insights into immunotherapeutic response and prognostic assessment in patients with colon adenocarcinoma (COAD). Methods: Univariate Cox proportional hazard analysis and Lasso regression analysis were performed to identify differentially expressed genes strongly associated with prognosis. Subsequently, a multifactorial model for prognostic risk assessment was developed using multiple Cox proportional hazard regression. Furthermore, we conducted comprehensive evaluations of the characteristics of disulfidptosis response-related LncRNAs, considering clinicopathological features, tumor microenvironment, and chemotherapy sensitivity. The expression levels of prognosis-related genes in COAD patients were validated using quantitative real-time fluorescence PCR (qRT-PCR). Additionally, the role of ZEB1-SA1 in colon cancer was investigated through CCK8 assays, wound healing experiment and transwell experiments. Results: disulfidptosis response-related LncRNAs were identified as robust predictors of COAD prognosis. Multifactorial analysis revealed that the risk score derived from these LncRNAs served as an independent prognostic factor for COAD. Patients in the low-risk group exhibited superior overall survival (OS) compared to those in the high-risk group. Accordingly, our developed Nomogram prediction model, integrating clinical characteristics and risk scores, demonstrated excellent prognostic efficacy. In vitro experiments demonstrated that ZEB1-SA1 promoted the proliferation and migration of COAD cells. Conclusion: Leveraging medical big data and artificial intelligence, we constructed a prediction model for disulfidptosis response-related LncRNAs based on the TCGA-COAD cohort, enabling accurate prognostic prediction in colon cancer patients. The implementation of this model in clinical practice can facilitate precise classification of COAD patients, identification of specific subgroups more likely to respond favorably to immunotherapy and chemotherapy, and inform the development of personalized treatment strategies for COAD patients based on scientific evidence.
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spelling pubmed-106175992023-11-01 Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms Chi, Hao Huang, Jinbang Yan, Yang Jiang, Chenglu Zhang, Shengke Chen, Haiqing Jiang, Lai Zhang, Jieying Zhang, Qinghong Yang, Guanhu Tian, Gang Front Mol Biosci Molecular Biosciences Background: Colon cancer, a prevalent and deadly malignancy worldwide, ranks as the third leading cause of cancer-related mortality. Disulfidptosis stress triggers a unique form of programmed cell death known as disulfidoptosis, characterized by excessive intracellular cystine accumulation. This study aimed to establish reliable bioindicators based on long non-coding RNAs (LncRNAs) associated with disulfidptosis-induced cell death, providing novel insights into immunotherapeutic response and prognostic assessment in patients with colon adenocarcinoma (COAD). Methods: Univariate Cox proportional hazard analysis and Lasso regression analysis were performed to identify differentially expressed genes strongly associated with prognosis. Subsequently, a multifactorial model for prognostic risk assessment was developed using multiple Cox proportional hazard regression. Furthermore, we conducted comprehensive evaluations of the characteristics of disulfidptosis response-related LncRNAs, considering clinicopathological features, tumor microenvironment, and chemotherapy sensitivity. The expression levels of prognosis-related genes in COAD patients were validated using quantitative real-time fluorescence PCR (qRT-PCR). Additionally, the role of ZEB1-SA1 in colon cancer was investigated through CCK8 assays, wound healing experiment and transwell experiments. Results: disulfidptosis response-related LncRNAs were identified as robust predictors of COAD prognosis. Multifactorial analysis revealed that the risk score derived from these LncRNAs served as an independent prognostic factor for COAD. Patients in the low-risk group exhibited superior overall survival (OS) compared to those in the high-risk group. Accordingly, our developed Nomogram prediction model, integrating clinical characteristics and risk scores, demonstrated excellent prognostic efficacy. In vitro experiments demonstrated that ZEB1-SA1 promoted the proliferation and migration of COAD cells. Conclusion: Leveraging medical big data and artificial intelligence, we constructed a prediction model for disulfidptosis response-related LncRNAs based on the TCGA-COAD cohort, enabling accurate prognostic prediction in colon cancer patients. The implementation of this model in clinical practice can facilitate precise classification of COAD patients, identification of specific subgroups more likely to respond favorably to immunotherapy and chemotherapy, and inform the development of personalized treatment strategies for COAD patients based on scientific evidence. Frontiers Media S.A. 2023-10-17 /pmc/articles/PMC10617599/ /pubmed/37916187 http://dx.doi.org/10.3389/fmolb.2023.1254232 Text en Copyright © 2023 Chi, Huang, Yan, Jiang, Zhang, Chen, Jiang, Zhang, Zhang, Yang and Tian. 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 Molecular Biosciences
Chi, Hao
Huang, Jinbang
Yan, Yang
Jiang, Chenglu
Zhang, Shengke
Chen, Haiqing
Jiang, Lai
Zhang, Jieying
Zhang, Qinghong
Yang, Guanhu
Tian, Gang
Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms
title Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms
title_full Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms
title_fullStr Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms
title_full_unstemmed Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms
title_short Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms
title_sort unraveling the role of disulfidptosis-related lncrnas in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617599/
https://www.ncbi.nlm.nih.gov/pubmed/37916187
http://dx.doi.org/10.3389/fmolb.2023.1254232
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