Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy
BackgroundTumor 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.MethodsWe enrolled 155...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1007146/full |
| _version_ | 1797961356336431104 |
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| author | Xiao-Peng Duan Ke Liu Xiao-Dong Jiao Bao-Dong Qin Bing Li Xi He Yan Ling Ying Wu Shi-Qi Chen Yuan-Sheng Zang |
| author_facet | Xiao-Peng Duan Ke Liu Xiao-Dong Jiao Bao-Dong Qin Bing Li Xi He Yan Ling Ying Wu Shi-Qi Chen Yuan-Sheng Zang |
| author_sort | Xiao-Peng Duan |
| collection | DOAJ |
| description | BackgroundTumor 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.MethodsWe 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.ResultsAmong 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.ConclusionsTMB-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. |
| first_indexed | 2024-04-11T00:57:16Z |
| format | Article |
| id | doaj.art-1322870e860343b38f91fa2776a89423 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T00:57:16Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-1322870e860343b38f91fa2776a894232023-01-04T22:54:08ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011210.3389/fonc.2022.10071461007146Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapyXiao-Peng Duan0Ke Liu1Xiao-Dong Jiao2Bao-Dong Qin3Bing Li4Xi He5Yan Ling6Ying Wu7Shi-Qi Chen8Yuan-Sheng Zang9Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaBurning Rock Biotech, Shanghai, ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, ChinaBackgroundTumor 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.MethodsWe 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.ResultsAmong 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.ConclusionsTMB-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.https://www.frontiersin.org/articles/10.3389/fonc.2022.1007146/fullgastric cancerchemotherapytumor mutation burdenbiomarkerprognostic valuemechanism |
| spellingShingle | Xiao-Peng Duan Ke Liu Xiao-Dong Jiao Bao-Dong Qin Bing Li Xi He Yan Ling Ying Wu Shi-Qi Chen Yuan-Sheng Zang Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy Frontiers in Oncology gastric cancer chemotherapy tumor mutation burden biomarker prognostic value mechanism |
| 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 | gastric cancer chemotherapy tumor mutation burden biomarker prognostic value mechanism |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1007146/full |
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