{"title":"Bioinformatics Analysis of Programmed Death-1-Trastuzumab Resistance Regulatory Networks in Breast Cancer Cells.","authors":"Adam Hermawan, Herwandhani Putri","doi":"10.31557/APJCP.2025.26.1.279","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Programmed cell death-1 (PD-1, encoded by PDCD1) regulatory network participates in glioblastoma multiforme development. However, such a network in trastuzumab-resistant human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains to be determined. Accordingly, this study was aimed to explore the PD-1 regulatory network responsible for the resistance of breast cancer cells to trastuzumab through a bioinformatics approach.</p><p><strong>Methods: </strong>The study used data mining tools like cBioportal and OMIM to identify genes involved in the programmed cell death-1-trastuzumab resistance regulatory network. The network was further examined using various tools like WebGestalt, DAVID, STRING, Cytoscape, CytoHubba, GEPIA, TNMPlot, and ROCPlot.</p><p><strong>Results: </strong>The PDCD1 regulatory network in trastuzumab-resistant HER2+ breast cancer is linked to Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), interleukin (IL)-10, protein tyrosine phosphatase receptor type C (PTPRC), and FCGR2B. These factors have a significant prognostic power in pathological complete response in breast cancer patients treated with trastuzumab. Infiltration of B cells, CD8+ cells, CD4+ cells, neutrophils, dendritic cells, macrophages, and regulatory T cells is directly correlated with PTR expression.</p><p><strong>Conclusion: </strong>The study identified four genes (CTLA4, IL10, PTPRC, and FCGR2B) that are linked to the regulatory network of PD-1 in trastuzumab-resistant HER2+ breast cancer cells. Further research is needed to develop the therapeutic target against trastuzumab resistance in HER2+ breast cancer.</p>","PeriodicalId":55451,"journal":{"name":"Asian Pacific Journal of Cancer Prevention","volume":"26 1","pages":"279-292"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Pacific Journal of Cancer Prevention","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31557/APJCP.2025.26.1.279","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Programmed cell death-1 (PD-1, encoded by PDCD1) regulatory network participates in glioblastoma multiforme development. However, such a network in trastuzumab-resistant human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains to be determined. Accordingly, this study was aimed to explore the PD-1 regulatory network responsible for the resistance of breast cancer cells to trastuzumab through a bioinformatics approach.
Methods: The study used data mining tools like cBioportal and OMIM to identify genes involved in the programmed cell death-1-trastuzumab resistance regulatory network. The network was further examined using various tools like WebGestalt, DAVID, STRING, Cytoscape, CytoHubba, GEPIA, TNMPlot, and ROCPlot.
Results: The PDCD1 regulatory network in trastuzumab-resistant HER2+ breast cancer is linked to Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), interleukin (IL)-10, protein tyrosine phosphatase receptor type C (PTPRC), and FCGR2B. These factors have a significant prognostic power in pathological complete response in breast cancer patients treated with trastuzumab. Infiltration of B cells, CD8+ cells, CD4+ cells, neutrophils, dendritic cells, macrophages, and regulatory T cells is directly correlated with PTR expression.
Conclusion: The study identified four genes (CTLA4, IL10, PTPRC, and FCGR2B) that are linked to the regulatory network of PD-1 in trastuzumab-resistant HER2+ breast cancer cells. Further research is needed to develop the therapeutic target against trastuzumab resistance in HER2+ breast cancer.
期刊介绍：
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation.
The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally.
The APJCP publishes original research results under the following categories:
-Epidemiology, detection and screening.
-Cellular research and bio-markers.
-Identification of bio-targets and agents with novel mechanisms of action.
-Optimal clinical use of existing anti-cancer agents, including combination therapies.
-Radiation and surgery.
-Palliative care.
-Patient adherence, quality of life, satisfaction.
-Health economic evaluations.
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