Bioinformatics Analysis of Programmed Death-1-Trastuzumab Resistance Regulatory Networks in Breast Cancer Cells.

Q2 Medicine Asian Pacific Journal of Cancer Prevention Pub Date : 2025-01-01 DOI:10.31557/APJCP.2025.26.1.279

Adam Hermawan, Herwandhani Putri

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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.

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乳腺癌细胞程序性死亡-1-曲妥珠单抗耐药调控网络的生物信息学分析

目的：由PDCD1编码的程序性细胞死亡-1 （Programmed cell death-1, PD-1）调控网络参与胶质母细胞瘤多形性发育。然而，这种网络在曲妥珠单抗耐药的人表皮生长因子受体2阳性（HER2+）乳腺癌中仍有待确定。因此，本研究旨在通过生物信息学方法探索乳腺癌细胞对曲妥珠单抗耐药的PD-1调控网络。方法：本研究使用cBioportal和OMIM等数据挖掘工具鉴定程序性细胞死亡-1-曲妥珠单抗耐药调控网络中涉及的基因。使用WebGestalt、DAVID、STRING、Cytoscape、CytoHubba、GEPIA、TNMPlot和ROCPlot等工具进一步检查该网络。结果：在曲妥珠单抗耐药的HER2+乳腺癌中，PDCD1调控网络与细胞毒性t淋巴细胞相关抗原4 （CTLA-4）、白细胞介素(IL)-10、蛋白酪氨酸磷酸酶受体C （PTPRC）和FCGR2B相关。这些因素在曲妥珠单抗治疗的乳腺癌患者的病理完全缓解中具有重要的预后作用。B细胞、CD8+细胞、CD4+细胞、中性粒细胞、树突状细胞、巨噬细胞和调节性T细胞的浸润与PTR表达直接相关。结论：本研究确定了4个基因（CTLA4、IL10、PTPRC和FCGR2B）在曲妥珠单抗耐药HER2+乳腺癌细胞中与PD-1调控网络相关。HER2阳性乳腺癌中抗曲妥珠单抗耐药的治疗靶点有待进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Asian Pacific Journal of Cancer Prevention 医学-肿瘤学

CiteScore

2.80

自引率

0.00%

发文量

779

审稿时长

3 months

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.