The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer
Objective: Currently, there is an urgent need to identify immunotherapeutic biomarkers to increase the benefit of immune checkpoint inhibitors (ICIs) for patients with gastric cancer (GC). Homologous recombination deficiency (HRD) can modify the tumor immune microenvironment by increasing the presen...
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| Format: | Article |
| Language: | English |
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China Anti-Cancer Association
2020-11-01
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| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | http://www.cancerbiomed.org/index.php/cocr/article/view/1697 |
| _version_ | 1818857383059783680 |
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| author | Yue Fan Haifeng Ying Xueying Wu Huan Chen Ying Hu Henghui Zhang Lijia Wu Ying Yang Beibei Mao Lan Zheng |
| author_facet | Yue Fan Haifeng Ying Xueying Wu Huan Chen Ying Hu Henghui Zhang Lijia Wu Ying Yang Beibei Mao Lan Zheng |
| author_sort | Yue Fan |
| collection | DOAJ |
| description | Objective: Currently, there is an urgent need to identify immunotherapeutic biomarkers to increase the benefit of immune checkpoint inhibitors (ICIs) for patients with gastric cancer (GC). Homologous recombination deficiency (HRD) can modify the tumor immune microenvironment by increasing the presence of tumor-infiltrating lymphocytes and therefore might serve as a biomarker of immunotherapeutic response. We aimed to analyze the mutational pattern of HR-associated genes in Chinese patients with GC and its relevance to the tumor immune profile and clinical immunotherapeutic response. Methods: A panel of 543 cancer-associated genes was used to analyze genomic profiles in a cohort comprising 484 Chinese patients with GC. Correlations between HR gene mutations and tumor immunity or clinical outcomes were identified via bioinformatic analysis using 2 GC genomic datasets (TCGA and MSK-IMPACT). Results: Fifty-one of the 484 (10.54%) patients carried at least one somatic mutation in an HR gene; ATM (16/484, 3.31%) was among the most frequently mutated HR genes in the Chinese cohort. Mutations in HR genes were associated with elevated tumor mutational burden, enhanced immune activity, and microsatellite instability status. In the MSK-IMPACT cohort comprising 49 patients with stomach adenocarcinoma or gastroesophageal junction adenocarcinoma treated with ICIs, patients with HR-mut GC (n = 12) had significantly better overall survival than those with HR-wt GC (n = 37) (log-rank test, P < 0.05). Conclusions: Our data suggest that detection of somatic mutations in HR genes might aid in identifying patients who might benefit from immune checkpoint blockade therapy. |
| first_indexed | 2024-12-19T08:39:31Z |
| format | Article |
| id | doaj.art-abb8684d37de4e9896bbcb244f44921b |
| institution | Directory Open Access Journal |
| issn | 2095-3941 |
| language | English |
| last_indexed | 2024-12-19T08:39:31Z |
| publishDate | 2020-11-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-abb8684d37de4e9896bbcb244f44921b2022-12-21T20:28:58ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412020-11-011741002101310.20892/j.issn.2095-3941.2020.0089The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancerYue Fan0Haifeng Ying1Xueying Wu2Huan Chen3Ying Hu4Henghui Zhang5Lijia Wu6Ying Yang7Beibei Mao8Lan Zheng9Department of integrated Traditional Chinese Medicine and Western Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, ChinaGenecast Precision Medicine Technology Institute, Beijing 100191, ChinaGenecast Precision Medicine Technology Institute, Beijing 100191, ChinaCenter of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaGenecast Precision Medicine Technology Institute, Beijing 100191, ChinaGenecast Precision Medicine Technology Institute, Beijing 100191, ChinaGenecast Precision Medicine Technology Institute, Beijing 100191, ChinaGenecast Precision Medicine Technology Institute, Beijing 100191, ChinaDepartment of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, ChinaObjective: Currently, there is an urgent need to identify immunotherapeutic biomarkers to increase the benefit of immune checkpoint inhibitors (ICIs) for patients with gastric cancer (GC). Homologous recombination deficiency (HRD) can modify the tumor immune microenvironment by increasing the presence of tumor-infiltrating lymphocytes and therefore might serve as a biomarker of immunotherapeutic response. We aimed to analyze the mutational pattern of HR-associated genes in Chinese patients with GC and its relevance to the tumor immune profile and clinical immunotherapeutic response. Methods: A panel of 543 cancer-associated genes was used to analyze genomic profiles in a cohort comprising 484 Chinese patients with GC. Correlations between HR gene mutations and tumor immunity or clinical outcomes were identified via bioinformatic analysis using 2 GC genomic datasets (TCGA and MSK-IMPACT). Results: Fifty-one of the 484 (10.54%) patients carried at least one somatic mutation in an HR gene; ATM (16/484, 3.31%) was among the most frequently mutated HR genes in the Chinese cohort. Mutations in HR genes were associated with elevated tumor mutational burden, enhanced immune activity, and microsatellite instability status. In the MSK-IMPACT cohort comprising 49 patients with stomach adenocarcinoma or gastroesophageal junction adenocarcinoma treated with ICIs, patients with HR-mut GC (n = 12) had significantly better overall survival than those with HR-wt GC (n = 37) (log-rank test, P < 0.05). Conclusions: Our data suggest that detection of somatic mutations in HR genes might aid in identifying patients who might benefit from immune checkpoint blockade therapy.http://www.cancerbiomed.org/index.php/cocr/article/view/1697gastric cancerhomologous recombination deficiencyimmunotherapybiomarker |
| spellingShingle | Yue Fan Haifeng Ying Xueying Wu Huan Chen Ying Hu Henghui Zhang Lijia Wu Ying Yang Beibei Mao Lan Zheng The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer Cancer Biology & Medicine gastric cancer homologous recombination deficiency immunotherapy biomarker |
| title | The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer |
| title_full | The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer |
| title_fullStr | The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer |
| title_full_unstemmed | The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer |
| title_short | The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer |
| title_sort | mutational pattern of homologous recombination hr associated genes and its relevance to the immunotherapeutic response in gastric cancer |
| topic | gastric cancer homologous recombination deficiency immunotherapy biomarker |
| url | http://www.cancerbiomed.org/index.php/cocr/article/view/1697 |
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