Cargando…

Development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma

Colon adenocarcinoma (COAD) is a common malignancy and has a high mortality rate. However, the current tumor node metastasis (TNM) staging system is inadequate for prognostic assessment of COAD patients. Therefore, there is an urgent need to identify reliable biomarkers for the prognosis COAD patien...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Miaomiao, Zhang, Tianyang, Chen, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639779/
https://www.ncbi.nlm.nih.gov/pubmed/36353119
http://dx.doi.org/10.3389/fgene.2022.1051800
_version_ 1784825708468502528
author Li, Miaomiao
Zhang, Tianyang
Chen, Wei
author_facet Li, Miaomiao
Zhang, Tianyang
Chen, Wei
author_sort Li, Miaomiao
collection PubMed
description Colon adenocarcinoma (COAD) is a common malignancy and has a high mortality rate. However, the current tumor node metastasis (TNM) staging system is inadequate for prognostic assessment of COAD patients. Therefore, there is an urgent need to identify reliable biomarkers for the prognosis COAD patients. The aberrant expression of necroptosis-related genes (NRGs) is reported to be associated with tumorigenesis and metastasis. In the present work, we compared the expression profiles of NRGs between COAD patients and normal individuals. Based on seven differentially expressed NRGs, a risk score was defined to predict the prognosis of COAD patients. The validation results from both training and independent external cohorts demonstrated that the risk score is able to distinguish the high and low risk COAD patients with higher accuracies, and is independent of the other clinical factors. To facilitate its clinical use, by integrating the proposed risk score, a nomogram was built to predict the risk of individual COAD patients. The C-index of the nomogram is 0.75, indicating the reliability of the nomogram in predicting survival rates. Furthermore, two candidate drugs, namely dapsone and xanthohumol, were screed out and validated by molecular docking, which hold the potential for the treatment of COAD. These results will provide novel clues for the diagnosis and treatment of COAD.
format Online
Article
Text
id pubmed-9639779
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96397792022-11-08 Development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma Li, Miaomiao Zhang, Tianyang Chen, Wei Front Genet Genetics Colon adenocarcinoma (COAD) is a common malignancy and has a high mortality rate. However, the current tumor node metastasis (TNM) staging system is inadequate for prognostic assessment of COAD patients. Therefore, there is an urgent need to identify reliable biomarkers for the prognosis COAD patients. The aberrant expression of necroptosis-related genes (NRGs) is reported to be associated with tumorigenesis and metastasis. In the present work, we compared the expression profiles of NRGs between COAD patients and normal individuals. Based on seven differentially expressed NRGs, a risk score was defined to predict the prognosis of COAD patients. The validation results from both training and independent external cohorts demonstrated that the risk score is able to distinguish the high and low risk COAD patients with higher accuracies, and is independent of the other clinical factors. To facilitate its clinical use, by integrating the proposed risk score, a nomogram was built to predict the risk of individual COAD patients. The C-index of the nomogram is 0.75, indicating the reliability of the nomogram in predicting survival rates. Furthermore, two candidate drugs, namely dapsone and xanthohumol, were screed out and validated by molecular docking, which hold the potential for the treatment of COAD. These results will provide novel clues for the diagnosis and treatment of COAD. Frontiers Media S.A. 2022-10-24 /pmc/articles/PMC9639779/ /pubmed/36353119 http://dx.doi.org/10.3389/fgene.2022.1051800 Text en Copyright © 2022 Li, Zhang and Chen. 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 Genetics
Li, Miaomiao
Zhang, Tianyang
Chen, Wei
Development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma
title Development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma
title_full Development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma
title_fullStr Development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma
title_full_unstemmed Development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma
title_short Development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma
title_sort development of necroptosis-related gene signature to predict the prognosis of colon adenocarcinoma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639779/
https://www.ncbi.nlm.nih.gov/pubmed/36353119
http://dx.doi.org/10.3389/fgene.2022.1051800
work_keys_str_mv AT limiaomiao developmentofnecroptosisrelatedgenesignaturetopredicttheprognosisofcolonadenocarcinoma
AT zhangtianyang developmentofnecroptosisrelatedgenesignaturetopredicttheprognosisofcolonadenocarcinoma
AT chenwei developmentofnecroptosisrelatedgenesignaturetopredicttheprognosisofcolonadenocarcinoma