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胰腺癌和胃癌的转化研究:博士论文中的一种方法学

Translational studies on pancreatic cancer and gastric cancer: a methodology in PhD thesis.

作者信息

Resell Mathilde, Qvigstad Gunnar, Wang Timothy C, Quante Anne S, González-Fernández África, Waldum Helge, Chen Duan, Zhao Chun-Mei

机构信息

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

Department of Medicine, St. Olavs University Hospital, Trondheim, Norway.

出版信息

Front Pharmacol. 2025 May 30;16:1604017. doi: 10.3389/fphar.2025.1604017. eCollection 2025.

DOI:10.3389/fphar.2025.1604017
PMID:40520180
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12162273/
Abstract

Pancreatic ductal adenocarcinoma (PDAC) and gastric adenocarcinoma (GA) are aggressive cancers with poor prognoses, demanding innovative approaches to advance treatment strategies and prevention efforts. This article presents a methodology in connection with PhD thesis on PDAC and GA, including motivation and knowledge in literature (Paper I), various research models (Paper II), knowledge discovery (Papers III and IV), and thesis assessment and evaluation (dissertation). The four studies aimed to address the gaps between patients and researchers and between basic and clinical research. Patient and Public Involvement (PPI) was explored to align research priorities with patients' needs. While PPI emphasized the importance of treatment-focused research, researchers and scientific journals prioritized basic science. Research guidance of "Findable, Accessible, Interoperable, and Reusable" (FAIR) was implanted in the studies, particularly proteomics datasets of different research models on PDAC. An analytic workflow for knowledge discovery with systems modeling was developed, leading to identification of translational targets of proteins and signaling networks on PDAC. Gastric intestinal metaplasia (GIM) is associated with GA. Multi-bioinformatics identified potential biomarkers for GA-related GIM, including genes and signaling networks. Potential repurposed drugs were also identified for both PDAC and GIM. In conclusion, the methodology was instructive in completing PhD thesis, whereas the findings in the original papers added new knowledge in translational research on PDAC and GA.

摘要

胰腺导管腺癌(PDAC)和胃腺癌(GA)是预后较差的侵袭性癌症,需要创新方法来推进治疗策略和预防工作。本文介绍了与关于PDAC和GA的博士论文相关的一种方法,包括文献中的动机和知识(论文一)、各种研究模型(论文二)、知识发现(论文三和论文四)以及论文评估与评价(学位论文)。这四项研究旨在弥合患者与研究人员之间以及基础研究与临床研究之间的差距。探索了患者和公众参与(PPI),以使研究重点与患者需求保持一致。虽然PPI强调了以治疗为重点的研究的重要性,但研究人员和科学期刊优先考虑基础科学。在这些研究中植入了“可查找、可访问、可互操作和可重用”(FAIR)的研究指南,特别是关于PDAC不同研究模型的蛋白质组学数据集。开发了一种用于通过系统建模进行知识发现的分析工作流程,从而确定了PDAC上蛋白质和信号网络的转化靶点。胃化生(GIM)与GA相关。多生物信息学确定了与GA相关的GIM的潜在生物标志物,包括基因和信号网络。还为PDAC和GIM确定了潜在的重新利用药物。总之,该方法对完成博士论文具有指导意义,而原始论文中的研究结果为PDAC和GA的转化研究增添了新知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/0ee0afdc4213/fphar-16-1604017-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/2375bdde754f/fphar-16-1604017-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/282bc3c707f9/fphar-16-1604017-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/b6f3b15f940f/fphar-16-1604017-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/107de652d4b9/fphar-16-1604017-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/5ec939c58dd1/fphar-16-1604017-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/54c054db4e20/fphar-16-1604017-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/0ee0afdc4213/fphar-16-1604017-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/2375bdde754f/fphar-16-1604017-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/282bc3c707f9/fphar-16-1604017-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/b6f3b15f940f/fphar-16-1604017-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/107de652d4b9/fphar-16-1604017-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/5ec939c58dd1/fphar-16-1604017-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/54c054db4e20/fphar-16-1604017-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f9/12162273/0ee0afdc4213/fphar-16-1604017-g007.jpg

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本文引用的文献

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Sci Data. 2025 Feb 14;12(1):266. doi: 10.1038/s41597-025-04522-x.
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Cancer statistics, 2025.2025年癌症统计数据。
CA Cancer J Clin. 2025 Jan-Feb;75(1):10-45. doi: 10.3322/caac.21871. Epub 2025 Jan 16.
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Multi-bioinformatics revealed potential biomarkers and repurposed drugs for gastric adenocarcinoma-related gastric intestinal metaplasia.多组学分析揭示胃腺癌相关肠上皮化生的潜在生物标志物和再利用药物。
NPJ Syst Biol Appl. 2024 Nov 4;10(1):127. doi: 10.1038/s41540-024-00455-0.
4
The road to a world-unified approach to the management of patients with gastric intestinal metaplasia: a review of current guidelines.通向胃黏膜肠上皮化生患者管理的全球统一方法之路:当前指南综述。
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Prioritizing drug targets by perturbing biological network response functions.通过干扰生物网络响应功能来优先考虑药物靶点。
PLoS Comput Biol. 2024 Jun 27;20(6):e1012195. doi: 10.1371/journal.pcbi.1012195. eCollection 2024 Jun.
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Gaps between needs of patient and public involvement and interests of researchers on pancreatic cancer.
Patient Educ Couns. 2024 Mar;120:108125. doi: 10.1016/j.pec.2023.108125. Epub 2023 Dec 20.
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Analysis of pharma R&D productivity - a new perspective needed.分析医药研发生产力——需要新视角。
Drug Discov Today. 2023 Oct;28(10):103726. doi: 10.1016/j.drudis.2023.103726. Epub 2023 Jul 26.
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Gastric cancer treatment: recent progress and future perspectives.胃癌治疗:最新进展与未来展望。
J Hematol Oncol. 2023 May 27;16(1):57. doi: 10.1186/s13045-023-01451-3.
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Acta Pharm Sin B. 2022 Jul;12(7):3049-3062. doi: 10.1016/j.apsb.2022.02.002. Epub 2022 Feb 11.