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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....

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Autores principales: Kim, Jeong Eun, Park, Song Ee, Kim, Hee Jun, Hwang, In Gyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
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.
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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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