Cargando…

Comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer

BACKGROUND: Cervical cancer (CC) is the leading cause of cancer-related death in women. A limited number of studies have investigated whether immune-prognostic features can be used to predict the prognosis of CC. This study aimed to develop an improved prognostic risk scoring model (PRSM) for CC bas...

Descripción completa

Detalles Bibliográficos
Autores principales: Pi, Ya-Nan, Guo, Jun-Nan, Lou, Ge, Cui, Bin-Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638517/
https://www.ncbi.nlm.nih.gov/pubmed/34852825
http://dx.doi.org/10.1186/s12935-021-02333-9
_version_ 1784608957129555968
author Pi, Ya-Nan
Guo, Jun-Nan
Lou, Ge
Cui, Bin-Bin
author_facet Pi, Ya-Nan
Guo, Jun-Nan
Lou, Ge
Cui, Bin-Bin
author_sort Pi, Ya-Nan
collection PubMed
description BACKGROUND: Cervical cancer (CC) is the leading cause of cancer-related death in women. A limited number of studies have investigated whether immune-prognostic features can be used to predict the prognosis of CC. This study aimed to develop an improved prognostic risk scoring model (PRSM) for CC based on immune-related genes (IRGs) to predict survival and determine the key prognostic IRGs. METHODS: We downloaded the gene expression profiles and clinical data of CC patients from the TCGA and GEO databases. The ESTIMATE algorithm was used to calculate the score for both immune and stromal cells. Differentially expressed genes (DEGs) in different subpopulations were analyzed by “Limma”. A weighted gene co-expression network analysis (WGCNA) was used to establish a DEG co-expression module related to the immune score. Immune-related gene pairs (IRGPs) were constructed, and univariate- and Lasso-Cox regression analyses were used to analyze prognosis and establish a PRSM. A log-rank test was used to verify the accuracy and consistency of the scoring model. Identification of the predicted key IRG was ensured by the application of functional enrichment, DisNor, protein–protein interactions (PPIs) and heatmap. Finally, we extracted the key prognostic immune-related genes from the gene expression data, validated the key genes by immunohistochemistry and analyzed the correlation between their expression and drug sensitivity. RESULTS: A new PRSM was developed based on 22 IRGPs. The prognosis of the low-risk group in the model group (P < 0.001) and validation group (P = 0.039) was significantly better than that in the high-risk group. Furthermore, M1 and M2 macrophages were highly expressed in the low-risk group. Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway were significantly enriched in the low-risk group. Three representative genes (CD80, CD28, and LCP2) were markers of CC prognosis. CD80 and CD28 may more prominent represent important indicators to improve patient prognosis. These key genes was positively correlated with drug sensitivity. Finally, we found that differences in the sensitivity to JNK inhibitors could be distinguished based on the use and risk grouping of this PRSM. CONCLUSIONS: The prognostic model based on the IRGs and key genes have potential clinical significance for predicting the prognosis of CC patients, providing a foundation for clinical prognosis judgment and individualized treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02333-9.
format Online
Article
Text
id pubmed-8638517
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-86385172021-12-03 Comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer Pi, Ya-Nan Guo, Jun-Nan Lou, Ge Cui, Bin-Bin Cancer Cell Int Primary Research BACKGROUND: Cervical cancer (CC) is the leading cause of cancer-related death in women. A limited number of studies have investigated whether immune-prognostic features can be used to predict the prognosis of CC. This study aimed to develop an improved prognostic risk scoring model (PRSM) for CC based on immune-related genes (IRGs) to predict survival and determine the key prognostic IRGs. METHODS: We downloaded the gene expression profiles and clinical data of CC patients from the TCGA and GEO databases. The ESTIMATE algorithm was used to calculate the score for both immune and stromal cells. Differentially expressed genes (DEGs) in different subpopulations were analyzed by “Limma”. A weighted gene co-expression network analysis (WGCNA) was used to establish a DEG co-expression module related to the immune score. Immune-related gene pairs (IRGPs) were constructed, and univariate- and Lasso-Cox regression analyses were used to analyze prognosis and establish a PRSM. A log-rank test was used to verify the accuracy and consistency of the scoring model. Identification of the predicted key IRG was ensured by the application of functional enrichment, DisNor, protein–protein interactions (PPIs) and heatmap. Finally, we extracted the key prognostic immune-related genes from the gene expression data, validated the key genes by immunohistochemistry and analyzed the correlation between their expression and drug sensitivity. RESULTS: A new PRSM was developed based on 22 IRGPs. The prognosis of the low-risk group in the model group (P < 0.001) and validation group (P = 0.039) was significantly better than that in the high-risk group. Furthermore, M1 and M2 macrophages were highly expressed in the low-risk group. Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway were significantly enriched in the low-risk group. Three representative genes (CD80, CD28, and LCP2) were markers of CC prognosis. CD80 and CD28 may more prominent represent important indicators to improve patient prognosis. These key genes was positively correlated with drug sensitivity. Finally, we found that differences in the sensitivity to JNK inhibitors could be distinguished based on the use and risk grouping of this PRSM. CONCLUSIONS: The prognostic model based on the IRGs and key genes have potential clinical significance for predicting the prognosis of CC patients, providing a foundation for clinical prognosis judgment and individualized treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02333-9. BioMed Central 2021-12-01 /pmc/articles/PMC8638517/ /pubmed/34852825 http://dx.doi.org/10.1186/s12935-021-02333-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Pi, Ya-Nan
Guo, Jun-Nan
Lou, Ge
Cui, Bin-Bin
Comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer
title Comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer
title_full Comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer
title_fullStr Comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer
title_full_unstemmed Comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer
title_short Comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer
title_sort comprehensive analysis of prognostic immune-related genes and drug sensitivity in cervical cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638517/
https://www.ncbi.nlm.nih.gov/pubmed/34852825
http://dx.doi.org/10.1186/s12935-021-02333-9
work_keys_str_mv AT piyanan comprehensiveanalysisofprognosticimmunerelatedgenesanddrugsensitivityincervicalcancer
AT guojunnan comprehensiveanalysisofprognosticimmunerelatedgenesanddrugsensitivityincervicalcancer
AT louge comprehensiveanalysisofprognosticimmunerelatedgenesanddrugsensitivityincervicalcancer
AT cuibinbin comprehensiveanalysisofprognosticimmunerelatedgenesanddrugsensitivityincervicalcancer