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Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy
Purpose: This study aimed to investigate the relationship between DNA damage response (DDR)-related protein expression and the clinical outcomes of patients with gastric cancer stage IV and recurrent advanced gastric cancer patients after gastrectomy treated with palliative first-line chemotherapy....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197943/ https://www.ncbi.nlm.nih.gov/pubmed/37215456 http://dx.doi.org/10.7150/jca.81632 |
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author | Kim, Jeong Eun Park, Song Ee Kim, Hee Jun Hwang, In Gyu |
author_facet | Kim, Jeong Eun Park, Song Ee Kim, Hee Jun Hwang, In Gyu |
author_sort | Kim, Jeong Eun |
collection | PubMed |
description | Purpose: This study aimed to investigate the relationship between DNA damage response (DDR)-related protein expression and the clinical outcomes of patients with gastric cancer stage IV and recurrent advanced gastric cancer patients after gastrectomy treated with palliative first-line chemotherapy. Materials and Methods: A total of 611 gastric cancer patients underwent D2 radical gastrectomy at Chung-Ang University Hospital between January 2005 and December 2017, of which 72 patients who received gastrectomy treatment with palliative chemotherapy were enrolled in this study. We performed the immunohistochemical assessment of MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded samples. In addition, Kaplan-Meier survival analysis and Cox regression models were used to evaluate independent predictors of overall survival (OS) and progression-free survival (PFS). Results: Among the 72 patients studied, immunohistochemical staining analysis indicated deficient DNA mismatch repair (dMMR) in 19.4% of patients (n = 14). The most common DDR gene with suppressed expression was PARP-1 (n = 41, 56.9%), followed by ATM (n = 26, 36.1%), ARID1A (n = 10, 13.9%), MLH1 (n = 12, 16.7%), BRCA1 (n = 11, 15.3%), and MSH2 (n = 3, 4.2%). HER2 (n = 6, 8.3%) and PD-L1 (n = 3, 4.2%) were expressed in 72 patients. The dMMR group exhibited a significantly longer median OS than the MMR proficient (pMMR) group (19.9 months vs. 11.0 months; hazard ratio [HR] 0.474, 95% confidence interval [CI] = 0.239-0.937, P = 0.032). The dMMR group exhibited a significantly longer median PFS than the pMMR group (7.0 months vs. 5.1 months; HR= 0.498, 95% CI = 0.267-0.928, P = 0.028). Conclusions: Of stage IV gastric cancer and recurrent gastric cancer patients who underwent gastrectomy, the dMMR group had a better survival rate than the pMMR group. Although dMMR is a predictive factor for immunotherapy in advanced gastric cancer, further studies are needed to determine whether it is a prognostic factor for gastric cancer patients treated with palliative cytotoxic chemotherapy. |
format | Online Article Text |
id | pubmed-10197943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-101979432023-05-20 Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy Kim, Jeong Eun Park, Song Ee Kim, Hee Jun Hwang, In Gyu J Cancer Research Paper Purpose: This study aimed to investigate the relationship between DNA damage response (DDR)-related protein expression and the clinical outcomes of patients with gastric cancer stage IV and recurrent advanced gastric cancer patients after gastrectomy treated with palliative first-line chemotherapy. Materials and Methods: A total of 611 gastric cancer patients underwent D2 radical gastrectomy at Chung-Ang University Hospital between January 2005 and December 2017, of which 72 patients who received gastrectomy treatment with palliative chemotherapy were enrolled in this study. We performed the immunohistochemical assessment of MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded samples. In addition, Kaplan-Meier survival analysis and Cox regression models were used to evaluate independent predictors of overall survival (OS) and progression-free survival (PFS). Results: Among the 72 patients studied, immunohistochemical staining analysis indicated deficient DNA mismatch repair (dMMR) in 19.4% of patients (n = 14). The most common DDR gene with suppressed expression was PARP-1 (n = 41, 56.9%), followed by ATM (n = 26, 36.1%), ARID1A (n = 10, 13.9%), MLH1 (n = 12, 16.7%), BRCA1 (n = 11, 15.3%), and MSH2 (n = 3, 4.2%). HER2 (n = 6, 8.3%) and PD-L1 (n = 3, 4.2%) were expressed in 72 patients. The dMMR group exhibited a significantly longer median OS than the MMR proficient (pMMR) group (19.9 months vs. 11.0 months; hazard ratio [HR] 0.474, 95% confidence interval [CI] = 0.239-0.937, P = 0.032). The dMMR group exhibited a significantly longer median PFS than the pMMR group (7.0 months vs. 5.1 months; HR= 0.498, 95% CI = 0.267-0.928, P = 0.028). Conclusions: Of stage IV gastric cancer and recurrent gastric cancer patients who underwent gastrectomy, the dMMR group had a better survival rate than the pMMR group. Although dMMR is a predictive factor for immunotherapy in advanced gastric cancer, further studies are needed to determine whether it is a prognostic factor for gastric cancer patients treated with palliative cytotoxic chemotherapy. Ivyspring International Publisher 2023-05-05 /pmc/articles/PMC10197943/ /pubmed/37215456 http://dx.doi.org/10.7150/jca.81632 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Kim, Jeong Eun Park, Song Ee Kim, Hee Jun Hwang, In Gyu Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy |
title | Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy |
title_full | Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy |
title_fullStr | Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy |
title_full_unstemmed | Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy |
title_short | Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy |
title_sort | clinical implication of dna damage response genes in advanced gastric cancer stage iv and recurrent gastric cancer patients after gastrectomy treated palliative chemotherapy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197943/ https://www.ncbi.nlm.nih.gov/pubmed/37215456 http://dx.doi.org/10.7150/jca.81632 |
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