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Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes
BACKGROUND: The incidence and mortality of pancreatic cancer are almost the same, and the 5-year survival rate is less than 10%. The high mortality of pancreatic cancer is related to chemo-radiotherapy. The present study aimed to establish a prognostic signature of pancreatic cancer based on chemo-r...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331760/ https://www.ncbi.nlm.nih.gov/pubmed/37435207 http://dx.doi.org/10.21037/jgo-23-308 |
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author | Sun, Hui Zhang, Weigang Chu, Yunqian Zhou, Lei Gong, Feiran Li, Wei Chen, Kai |
author_facet | Sun, Hui Zhang, Weigang Chu, Yunqian Zhou, Lei Gong, Feiran Li, Wei Chen, Kai |
author_sort | Sun, Hui |
collection | PubMed |
description | BACKGROUND: The incidence and mortality of pancreatic cancer are almost the same, and the 5-year survival rate is less than 10%. The high mortality of pancreatic cancer is related to chemo-radiotherapy. The present study aimed to establish a prognostic signature of pancreatic cancer based on chemo-radiotherapy resistant-related genes (CRRGs). METHODS: In this study, we explored the radiation-resistant and chemotherapy-resistant pancreatic cancer cell lines by colony formation and a subcutaneous tumor model in nude mice. Next, we obtained CRRGs from radiation- and gemcitabine-resistant pancreatic cancer cell lines in the Gene Expression Omnibus (GEO) database. Based on univariate Cox and least absolute shrinkage and selection operator (LASSO) Cox regression analyses, a prognostic model of the pancreatic adenocarcinoma (PAAD) cohort in The Cancer Genome Atlas (TCGA) database (N=177) was established and verified using the GEO cohort data set (N=112). Finally, the functions of candidate target genes were verified by a methyl thiazolyl tetrazolium (MTT) assay, a colony formation assay, and a subcutaneous tumor model in nude mice. RESULTS: Through the in vitro and in vivo experiments, we found that radiotherapy- and chemotherapy-resistant pancreatic cancer cells were cross-resistant to chemotherapy and radiotherapy. We constructed a risk model consisting of nine CRRGs (SNAP25, GPR87, DLL1, LAD1, WASF3, ARHGAP29, ZBED2, GAD1, and JAG1) by using public databases. According to the Kaplan-Meier curve analysis, the survival of the high-risk group was worse than that of the low-risk group. We then used nomograms to predict the 1/3/5-year overall survival (OS) in pancreatic cancer patients. We chose JAG1 as a candidate target since it has been proven to be involved in the stemness maintenance of cancer cells, and found that JAG1 silencing inhibited the proliferation and chemo-radiotherapy tolerance of pancreatic cancer cells. CONCLUSIONS: This study established and validated a prognostic signature of pancreatic cancer using nine CRRGs. The in vitro and in vivo experiments showed that JAG1 could promote the proliferation and chemoradiotherapy tolerance of pancreatic cancer cell lines. These findings may offer new insights into the role of CRRGs in pancreatic cancer and provide novel prognostic biomarkers for the treatment of pancreatic cancer. |
format | Online Article Text |
id | pubmed-10331760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-103317602023-07-11 Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes Sun, Hui Zhang, Weigang Chu, Yunqian Zhou, Lei Gong, Feiran Li, Wei Chen, Kai J Gastrointest Oncol Original Article BACKGROUND: The incidence and mortality of pancreatic cancer are almost the same, and the 5-year survival rate is less than 10%. The high mortality of pancreatic cancer is related to chemo-radiotherapy. The present study aimed to establish a prognostic signature of pancreatic cancer based on chemo-radiotherapy resistant-related genes (CRRGs). METHODS: In this study, we explored the radiation-resistant and chemotherapy-resistant pancreatic cancer cell lines by colony formation and a subcutaneous tumor model in nude mice. Next, we obtained CRRGs from radiation- and gemcitabine-resistant pancreatic cancer cell lines in the Gene Expression Omnibus (GEO) database. Based on univariate Cox and least absolute shrinkage and selection operator (LASSO) Cox regression analyses, a prognostic model of the pancreatic adenocarcinoma (PAAD) cohort in The Cancer Genome Atlas (TCGA) database (N=177) was established and verified using the GEO cohort data set (N=112). Finally, the functions of candidate target genes were verified by a methyl thiazolyl tetrazolium (MTT) assay, a colony formation assay, and a subcutaneous tumor model in nude mice. RESULTS: Through the in vitro and in vivo experiments, we found that radiotherapy- and chemotherapy-resistant pancreatic cancer cells were cross-resistant to chemotherapy and radiotherapy. We constructed a risk model consisting of nine CRRGs (SNAP25, GPR87, DLL1, LAD1, WASF3, ARHGAP29, ZBED2, GAD1, and JAG1) by using public databases. According to the Kaplan-Meier curve analysis, the survival of the high-risk group was worse than that of the low-risk group. We then used nomograms to predict the 1/3/5-year overall survival (OS) in pancreatic cancer patients. We chose JAG1 as a candidate target since it has been proven to be involved in the stemness maintenance of cancer cells, and found that JAG1 silencing inhibited the proliferation and chemo-radiotherapy tolerance of pancreatic cancer cells. CONCLUSIONS: This study established and validated a prognostic signature of pancreatic cancer using nine CRRGs. The in vitro and in vivo experiments showed that JAG1 could promote the proliferation and chemoradiotherapy tolerance of pancreatic cancer cell lines. These findings may offer new insights into the role of CRRGs in pancreatic cancer and provide novel prognostic biomarkers for the treatment of pancreatic cancer. AME Publishing Company 2023-06-19 2023-06-30 /pmc/articles/PMC10331760/ /pubmed/37435207 http://dx.doi.org/10.21037/jgo-23-308 Text en 2023 Journal of Gastrointestinal Oncology. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Sun, Hui Zhang, Weigang Chu, Yunqian Zhou, Lei Gong, Feiran Li, Wei Chen, Kai Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes |
title | Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes |
title_full | Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes |
title_fullStr | Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes |
title_full_unstemmed | Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes |
title_short | Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes |
title_sort | prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331760/ https://www.ncbi.nlm.nih.gov/pubmed/37435207 http://dx.doi.org/10.21037/jgo-23-308 |
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