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Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy
BACKGROUND: Tumor mutation burden (TMB) is a promising biomarker positively associated with the benefit of immunotherapy and that might predict the outcome of chemotherapy. We described the prognostic value of TMB in advanced gastric cancer and explored the underlying mechanism. METHODS: We enrolled...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9847361/ https://www.ncbi.nlm.nih.gov/pubmed/36686739 http://dx.doi.org/10.3389/fonc.2022.1007146 |
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author | Duan, Xiao-Peng Liu, Ke Jiao, Xiao-Dong Qin, Bao-Dong Li, Bing He, Xi Ling, Yan Wu, Ying Chen, Shi-Qi Zang, Yuan-Sheng |
author_facet | Duan, Xiao-Peng Liu, Ke Jiao, Xiao-Dong Qin, Bao-Dong Li, Bing He, Xi Ling, Yan Wu, Ying Chen, Shi-Qi Zang, Yuan-Sheng |
author_sort | Duan, Xiao-Peng |
collection | PubMed |
description | BACKGROUND: Tumor mutation burden (TMB) is a promising biomarker positively associated with the benefit of immunotherapy and that might predict the outcome of chemotherapy. We described the prognostic value of TMB in advanced gastric cancer and explored the underlying mechanism. METHODS: We enrolled 155 TMB-evaluated advanced gastric cancer patients and analyzed the relationship between clinicopathological characteristics and both overall survival (OS) and progression-free survival (PFS) among 40 patients treated with first-line chemotherapy. We further verified the distribution of TMB and analyzed the potential mechanism underlying the prognosis based on The Cancer Genome Atlas (TCGA) database. RESULTS: Among the 155 patients, 29 (18.7%) were TMB-high (TMB ≥ 10), roughly the same as the proportion in the TCGA data. Of the 40 patients receiving first-line chemotherapy, the median OS (7.9 vs. 12.1 months; HR 3.18; p = 0.0056) and PFS (4.4 vs. 6.2 months; HR 2.94; p = 0.0099) of the tissue-tested TMB (tTMB)-high patients were inferior to those of the tTMB-low patients. Similarly, unfavorable median OS (9.9 vs. 12.1 months; HR 2.11; p = 0.028) and PFS (5.3 vs. 6.5 months; HR 2.49; p = 0.0054) were shown in the blood-tested TMB (bTMB)-high than in the bTMB-low patients. The Cox analysis demonstrated that both tTMB-high and bTMB-high were significant independent predictors of dreadful OS and PFS. The differentially expressed genes (DEGs) according to TMB status were most significantly enriched in the downregulated metabolic pathway among the TMB-high patients. CONCLUSIONS: TMB-high advanced gastric cancer patients accounted for around one-sixth and had a poorer prognosis than TMB-low patients when treated with first-line chemotherapy. The potential mechanism might be the downregulated metabolic activity in TMB-high patients. |
format | Online Article Text |
id | pubmed-9847361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98473612023-01-19 Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy Duan, Xiao-Peng Liu, Ke Jiao, Xiao-Dong Qin, Bao-Dong Li, Bing He, Xi Ling, Yan Wu, Ying Chen, Shi-Qi Zang, Yuan-Sheng Front Oncol Oncology BACKGROUND: Tumor mutation burden (TMB) is a promising biomarker positively associated with the benefit of immunotherapy and that might predict the outcome of chemotherapy. We described the prognostic value of TMB in advanced gastric cancer and explored the underlying mechanism. METHODS: We enrolled 155 TMB-evaluated advanced gastric cancer patients and analyzed the relationship between clinicopathological characteristics and both overall survival (OS) and progression-free survival (PFS) among 40 patients treated with first-line chemotherapy. We further verified the distribution of TMB and analyzed the potential mechanism underlying the prognosis based on The Cancer Genome Atlas (TCGA) database. RESULTS: Among the 155 patients, 29 (18.7%) were TMB-high (TMB ≥ 10), roughly the same as the proportion in the TCGA data. Of the 40 patients receiving first-line chemotherapy, the median OS (7.9 vs. 12.1 months; HR 3.18; p = 0.0056) and PFS (4.4 vs. 6.2 months; HR 2.94; p = 0.0099) of the tissue-tested TMB (tTMB)-high patients were inferior to those of the tTMB-low patients. Similarly, unfavorable median OS (9.9 vs. 12.1 months; HR 2.11; p = 0.028) and PFS (5.3 vs. 6.5 months; HR 2.49; p = 0.0054) were shown in the blood-tested TMB (bTMB)-high than in the bTMB-low patients. The Cox analysis demonstrated that both tTMB-high and bTMB-high were significant independent predictors of dreadful OS and PFS. The differentially expressed genes (DEGs) according to TMB status were most significantly enriched in the downregulated metabolic pathway among the TMB-high patients. CONCLUSIONS: TMB-high advanced gastric cancer patients accounted for around one-sixth and had a poorer prognosis than TMB-low patients when treated with first-line chemotherapy. The potential mechanism might be the downregulated metabolic activity in TMB-high patients. Frontiers Media S.A. 2023-01-04 /pmc/articles/PMC9847361/ /pubmed/36686739 http://dx.doi.org/10.3389/fonc.2022.1007146 Text en Copyright © 2023 Duan, Liu, Jiao, Qin, Li, He, Ling, Wu, Chen and Zang 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 | Oncology Duan, Xiao-Peng Liu, Ke Jiao, Xiao-Dong Qin, Bao-Dong Li, Bing He, Xi Ling, Yan Wu, Ying Chen, Shi-Qi Zang, Yuan-Sheng Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy |
title | Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy |
title_full | Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy |
title_fullStr | Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy |
title_full_unstemmed | Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy |
title_short | Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy |
title_sort | prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9847361/ https://www.ncbi.nlm.nih.gov/pubmed/36686739 http://dx.doi.org/10.3389/fonc.2022.1007146 |
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