Characterization of immune microenvironment identifies prognostic and immunotherapy benefit for trastuzumab-based therapy
Background and Purpose: The tumor immune microenvironment (TIME) of breast cancer with positive human epidermal growth factor receptor 2 (HER2) is significantly related to the efficacy of trastuzumab, indicating the clinical potential of immunocheckpoint therapy combined with trastuzumab. This study...
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| Format: | Article |
| Language: | English |
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Editorial Office of China Oncology
2023-05-01
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| Series: | Zhongguo aizheng zazhi |
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| Online Access: | http://www.china-oncology.com/fileup/1007-3639/PDF/1686896442431-1211872650.pdf |
| _version_ | 1797794702878048256 |
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| author | YANG Wenxiao, GUO Linwei, LING Hong, HU Xin |
| author_facet | YANG Wenxiao, GUO Linwei, LING Hong, HU Xin |
| author_sort | YANG Wenxiao, GUO Linwei, LING Hong, HU Xin |
| collection | DOAJ |
| description | Background and Purpose: The tumor immune microenvironment (TIME) of breast cancer with positive human epidermal growth factor receptor 2 (HER2) is significantly related to the efficacy of trastuzumab, indicating the clinical potential of immunocheckpoint therapy combined with trastuzumab. This study aimed to explore the predictors of HER2-positive breast cancer combination therapy and screen the potential beneficiaries of combination therapy. Methods: Transcriptome and genome data of 509 HER2-positive breast cancer samples of patients receiving trastuzumab treatment from Gene Expression Omnibus (GEO) database and 67 HER2-positive breast cancer samples from The Cancer Genome Atlas (TCGA) databases were collected. Trastuzumab-resistant group’s differentially expressed genes were identified and analyzed for functional enrichment and protein-protein interaction. The log-rank test and multivariate COX proportional hazards regression were used with clinical data to create the prediction model. The TIME landscape was characterized using the CIBERSORT. The immunotherapy benefit was valued by the tumor immune dysfunction and exclusion (TIDE) score. Results: The trastuzumab related genetic prognostic index (TRGPI) consisting of four hub genes (GATA6, TRPV6, AMACR, ZHX2) was constructed by analyzing the immune microenvironment and gene expression characteristics between trastuzumab-remission group and trastuzumab-resistance group. Importantly, the results revealed that patients with lower TRPGI were trastuzumab-sensitive and more likely to benefit from immunotherapy because of the increased percentages of CD8+ T cells, active natural killer cells and programmed death-1 (PD-1) expression. Conclusion: This study redefined the benefit population through TIME and provided a selectable strategy of trastuzumab plus immunotherapy for HER2-positive breast cancer. |
| first_indexed | 2024-03-13T03:06:47Z |
| format | Article |
| id | doaj.art-6f6bd972d1834ecab5d76fe41b683f86 |
| institution | Directory Open Access Journal |
| issn | 1007-3639 |
| language | English |
| last_indexed | 2024-03-13T03:06:47Z |
| publishDate | 2023-05-01 |
| publisher | Editorial Office of China Oncology |
| record_format | Article |
| series | Zhongguo aizheng zazhi |
| spelling | doaj.art-6f6bd972d1834ecab5d76fe41b683f862023-06-27T00:54:53ZengEditorial Office of China OncologyZhongguo aizheng zazhi1007-36392023-05-0133548449810.19401/j.cnki.1007-3639.2023.05.009Characterization of immune microenvironment identifies prognostic and immunotherapy benefit for trastuzumab-based therapyYANG Wenxiao, GUO Linwei, LING Hong, HU Xin01. Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China;2. Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China;3. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaBackground and Purpose: The tumor immune microenvironment (TIME) of breast cancer with positive human epidermal growth factor receptor 2 (HER2) is significantly related to the efficacy of trastuzumab, indicating the clinical potential of immunocheckpoint therapy combined with trastuzumab. This study aimed to explore the predictors of HER2-positive breast cancer combination therapy and screen the potential beneficiaries of combination therapy. Methods: Transcriptome and genome data of 509 HER2-positive breast cancer samples of patients receiving trastuzumab treatment from Gene Expression Omnibus (GEO) database and 67 HER2-positive breast cancer samples from The Cancer Genome Atlas (TCGA) databases were collected. Trastuzumab-resistant group’s differentially expressed genes were identified and analyzed for functional enrichment and protein-protein interaction. The log-rank test and multivariate COX proportional hazards regression were used with clinical data to create the prediction model. The TIME landscape was characterized using the CIBERSORT. The immunotherapy benefit was valued by the tumor immune dysfunction and exclusion (TIDE) score. Results: The trastuzumab related genetic prognostic index (TRGPI) consisting of four hub genes (GATA6, TRPV6, AMACR, ZHX2) was constructed by analyzing the immune microenvironment and gene expression characteristics between trastuzumab-remission group and trastuzumab-resistance group. Importantly, the results revealed that patients with lower TRPGI were trastuzumab-sensitive and more likely to benefit from immunotherapy because of the increased percentages of CD8+ T cells, active natural killer cells and programmed death-1 (PD-1) expression. Conclusion: This study redefined the benefit population through TIME and provided a selectable strategy of trastuzumab plus immunotherapy for HER2-positive breast cancer.http://www.china-oncology.com/fileup/1007-3639/PDF/1686896442431-1211872650.pdf|tumor immune microenvironment|trastuzumab|immunotherapy|human epidermal growth factor receptor 2-positive breast cancer|prediction model |
| spellingShingle | YANG Wenxiao, GUO Linwei, LING Hong, HU Xin Characterization of immune microenvironment identifies prognostic and immunotherapy benefit for trastuzumab-based therapy Zhongguo aizheng zazhi |tumor immune microenvironment|trastuzumab|immunotherapy|human epidermal growth factor receptor 2-positive breast cancer|prediction model |
| title | Characterization of immune microenvironment identifies prognostic and immunotherapy benefit for trastuzumab-based therapy |
| title_full | Characterization of immune microenvironment identifies prognostic and immunotherapy benefit for trastuzumab-based therapy |
| title_fullStr | Characterization of immune microenvironment identifies prognostic and immunotherapy benefit for trastuzumab-based therapy |
| title_full_unstemmed | Characterization of immune microenvironment identifies prognostic and immunotherapy benefit for trastuzumab-based therapy |
| title_short | Characterization of immune microenvironment identifies prognostic and immunotherapy benefit for trastuzumab-based therapy |
| title_sort | characterization of immune microenvironment identifies prognostic and immunotherapy benefit for trastuzumab based therapy |
| topic | |tumor immune microenvironment|trastuzumab|immunotherapy|human epidermal growth factor receptor 2-positive breast cancer|prediction model |
| url | http://www.china-oncology.com/fileup/1007-3639/PDF/1686896442431-1211872650.pdf |
| work_keys_str_mv | AT yangwenxiaoguolinweilinghonghuxin characterizationofimmunemicroenvironmentidentifiesprognosticandimmunotherapybenefitfortrastuzumabbasedtherapy |