Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis
Qin Huo, Lvwen Ning, Ni Xie Biobank, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of ChinaCorrespondence: Ni Xie, Biobank, Shenzhen Institute...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-03-01
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| Series: | Breast Cancer: Targets and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/identification-of-gzma-as-a-potential-therapeutic-target-involved-in-i-peer-reviewed-fulltext-article-BCTT |
| _version_ | 1811154200628822016 |
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| author | Huo Q Ning L Xie N |
| author_facet | Huo Q Ning L Xie N |
| author_sort | Huo Q |
| collection | DOAJ |
| description | Qin Huo, Lvwen Ning, Ni Xie Biobank, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of ChinaCorrespondence: Ni Xie, Biobank, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, No. 3002 Sungang West Road, Futian District, Shenzhen, 518035, People’s Republic of China, Tel +86 1 350 158 0802, Fax +86 7 558 300 3435, Email xn100@szu.edu.cnPurpose: Granzyme A (GZMA) is a potential prognostic target for various cancer types. However, its therapeutic significance in breast cancer with immune infiltration remains controversial. We analyzed GZMA expression and its prognostic value in breast cancer with immune cell infiltration.Patients and methods: Data was obtained from patients with breast cancer registered at The Cancer Genome Atlas. A correlation was performed between GZMA expression and patient’s clinicopathological features such as age, pathologic stage, metastasis stage, overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI). Kaplan-Meier analyses and Cox proportional hazard regression model were used to examine the predictive significance of GZMA expression for breast cancer. The co-expression pattern of GZMA was assessed by the LinkedOmics web portal. The relationship between GZMA expression and immune cells was analyzed using the TIMER database. The correlation between GZMA and lymphocytes and immunomodulators was established with the TISIDB database.Results: There was a lower GZMA expression in breast cancer tissue than in normal tissue. Interestingly, GZMA expression was associated with age, pathologic stage, and the Tumour, Node, and Metastasis stage. Overexpression of GZMA was also associated with better OS, DSS, and PFI. Based on the Cox regression analysis, GZMA was identified as an independent favorable prognostic factor for breast cancer. Our findings demonstrated a strong association between GZMA and T-cell checkpoints (PD-1, PD-L1, and cytotoxic T lymphocyte-associated antigen (CTLA-4)) in breast cancer. Moreover, we evaluated the interactions between GZMA expression and markers of dendritic and CD8+ T cells using quantitative immunofluorescence. We discovered that increased infiltration of dendritic and CD8+ T cells was associated with GZMA expression in breast cancer.Conclusion: GZMA expression is associated with a favorable prognosis in breast cancer and is significantly correlated with immune cell infiltration. GZMA may be considered a promising therapeutic target for patients with breast cancer.Keywords: GZMA, expression, prognostic factor, immune infiltration, breast cancer |
| first_indexed | 2024-04-10T04:12:47Z |
| format | Article |
| id | doaj.art-7bbeee2dc033458e9228275ea1cb6826 |
| institution | Directory Open Access Journal |
| issn | 1179-1314 |
| language | English |
| last_indexed | 2024-04-10T04:12:47Z |
| publishDate | 2023-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Breast Cancer: Targets and Therapy |
| spelling | doaj.art-7bbeee2dc033458e9228275ea1cb68262023-03-12T15:18:22ZengDove Medical PressBreast Cancer: Targets and Therapy1179-13142023-03-01Volume 1521322682171Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical AnalysisHuo QNing LXie NQin Huo, Lvwen Ning, Ni Xie Biobank, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of ChinaCorrespondence: Ni Xie, Biobank, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, No. 3002 Sungang West Road, Futian District, Shenzhen, 518035, People’s Republic of China, Tel +86 1 350 158 0802, Fax +86 7 558 300 3435, Email xn100@szu.edu.cnPurpose: Granzyme A (GZMA) is a potential prognostic target for various cancer types. However, its therapeutic significance in breast cancer with immune infiltration remains controversial. We analyzed GZMA expression and its prognostic value in breast cancer with immune cell infiltration.Patients and methods: Data was obtained from patients with breast cancer registered at The Cancer Genome Atlas. A correlation was performed between GZMA expression and patient’s clinicopathological features such as age, pathologic stage, metastasis stage, overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI). Kaplan-Meier analyses and Cox proportional hazard regression model were used to examine the predictive significance of GZMA expression for breast cancer. The co-expression pattern of GZMA was assessed by the LinkedOmics web portal. The relationship between GZMA expression and immune cells was analyzed using the TIMER database. The correlation between GZMA and lymphocytes and immunomodulators was established with the TISIDB database.Results: There was a lower GZMA expression in breast cancer tissue than in normal tissue. Interestingly, GZMA expression was associated with age, pathologic stage, and the Tumour, Node, and Metastasis stage. Overexpression of GZMA was also associated with better OS, DSS, and PFI. Based on the Cox regression analysis, GZMA was identified as an independent favorable prognostic factor for breast cancer. Our findings demonstrated a strong association between GZMA and T-cell checkpoints (PD-1, PD-L1, and cytotoxic T lymphocyte-associated antigen (CTLA-4)) in breast cancer. Moreover, we evaluated the interactions between GZMA expression and markers of dendritic and CD8+ T cells using quantitative immunofluorescence. We discovered that increased infiltration of dendritic and CD8+ T cells was associated with GZMA expression in breast cancer.Conclusion: GZMA expression is associated with a favorable prognosis in breast cancer and is significantly correlated with immune cell infiltration. GZMA may be considered a promising therapeutic target for patients with breast cancer.Keywords: GZMA, expression, prognostic factor, immune infiltration, breast cancerhttps://www.dovepress.com/identification-of-gzma-as-a-potential-therapeutic-target-involved-in-i-peer-reviewed-fulltext-article-BCTTgzmaexpressionprognostic factorimmune infiltrationbreast cancer |
| spellingShingle | Huo Q Ning L Xie N Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis Breast Cancer: Targets and Therapy gzma expression prognostic factor immune infiltration breast cancer |
| title | Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis |
| title_full | Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis |
| title_fullStr | Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis |
| title_full_unstemmed | Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis |
| title_short | Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis |
| title_sort | identification of gzma as a potential therapeutic target involved in immune infiltration in breast cancer by integrated bioinformatical analysis |
| topic | gzma expression prognostic factor immune infiltration breast cancer |
| url | https://www.dovepress.com/identification-of-gzma-as-a-potential-therapeutic-target-involved-in-i-peer-reviewed-fulltext-article-BCTT |
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