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局部前列腺癌的蛋白质组学和磷酸化蛋白质组学全景揭示了不同的分子亚型，并深入了解精准治疗。

Proteomic and phosphoproteomic landscape of localized prostate cancer unveils distinct molecular subtypes and insights into precision therapeutics.

机构信息

Department of Urology, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai 200433, China.

Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.

出版信息

Proc Natl Acad Sci U S A. 2024 Oct;121(40):e2402741121. doi: 10.1073/pnas.2402741121. Epub 2024 Sep 25.

DOI:10.1073/pnas.2402741121
PMID:39320917
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11459144/
Abstract

Building upon our previous investigation of genomic, epigenomic, and transcriptomic profiles of prostate cancer in China, we conducted a comprehensive analysis of proteomic and phosphoproteomic profiles of 82 tumor tissues and matched adjacent normal tissues from 41 Chinese patients with localized prostate cancer. We identified three distinct proteomic subtypes with significant difference in both molecular features and clinical prognosis. Notably, these proteomic subtypes exhibited a parallel degree of heterogeneity in the phosphoproteome, featuring unique metabolism, proliferation, and immune infiltration characteristics. We further demonstrated that a combination of proteins and phosphosites serves as the most effective biomarkers in prostate cancer to predict biochemical recurrence. Through an integrated multiomics analysis, we revealed mechanistic differences underlying different proteomic subtypes and highlighted the potential significance of Serine/arginine-rich splicing factor 1 (SRSF1) phosphorylation in promoting the malignant characteristics of prostate cancer cells. Our multiomics data provide valuable resources for understanding the molecular mechanisms of prostate cancer within the Chinese population, which have the potential to inform the development of personalized treatment strategies and enhance prognostic analyses for prostate cancer patients.

摘要

在我们之前对中国前列腺癌的基因组、表观基因组和转录组谱进行研究的基础上，我们对 41 名中国局限性前列腺癌患者的 82 个肿瘤组织和匹配的相邻正常组织进行了蛋白质组学和磷酸化蛋白质组学的全面分析。我们发现了三种具有明显差异的蛋白质组亚型，在分子特征和临床预后方面都存在显著差异。值得注意的是，这些蛋白质组亚型在磷酸化蛋白质组中表现出平行程度的异质性，具有独特的代谢、增殖和免疫浸润特征。我们进一步证明，蛋白质和磷酸化位点的组合是预测前列腺癌生化复发的最有效生物标志物。通过综合多组学分析，我们揭示了不同蛋白质组亚型背后的机制差异，并强调丝氨酸/精氨酸丰富剪接因子 1（SRSF1）磷酸化在促进前列腺癌细胞恶性特征方面的潜在意义。我们的多组学数据为了解中国人群中前列腺癌的分子机制提供了有价值的资源，这些资源有可能为制定个性化治疗策略和增强前列腺癌患者的预后分析提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/2ec9a19590b1/pnas.2402741121fig08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/9dd2a7fc8755/pnas.2402741121fig01.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/c1f7c13372e5/pnas.2402741121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/7f881ed4687c/pnas.2402741121fig04.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/23cef5480469/pnas.2402741121fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/ef66dd097283/pnas.2402741121fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/2ec9a19590b1/pnas.2402741121fig08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/9dd2a7fc8755/pnas.2402741121fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/2c797dfd1dac/pnas.2402741121fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/c1f7c13372e5/pnas.2402741121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/7f881ed4687c/pnas.2402741121fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/870a57f3b346/pnas.2402741121fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/23cef5480469/pnas.2402741121fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/ef66dd097283/pnas.2402741121fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2480/11459144/2ec9a19590b1/pnas.2402741121fig08.jpg

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本文引用的文献

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Proteomic-based stratification of intermediate-risk prostate cancer patients.基于蛋白质组学的中危前列腺癌患者分层。
Life Sci Alliance. 2023 Dec 4;7(2). doi: 10.26508/lsa.202302146. Print 2024 Feb.
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Integrative proteomic characterization of adenocarcinoma of esophagogastric junction.胃食管结合部腺癌的综合蛋白质组学特征分析。
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Control of protein stability by post-translational modifications.蛋白质翻译后修饰对其稳定性的调控。
使用PTM-POSE对剪接对蛋白质异构体翻译后修饰多样性的影响进行系统分析。
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Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as an AMPK substrate regulating skeletal muscle function.三种运动方式的磷酸蛋白质组学鉴定出经典信号通路和 C18ORF25 作为 AMPK 底物，调节骨骼肌功能。
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Cancer statistics in China and United States, 2022: profiles, trends, and determinants.中国和美国 2022 年癌症统计数据：概况、趋势和决定因素。
Chin Med J (Engl). 2022 Feb 9;135(5):584-590. doi: 10.1097/CM9.0000000000002108.
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Phosphoproteomics reveals therapeutic targets of esophageal squamous cell carcinoma.磷酸化蛋白质组学揭示食管鳞状细胞癌的治疗靶点。
Signal Transduct Target Ther. 2021 Nov 12;6(1):381. doi: 10.1038/s41392-021-00682-5.
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