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通过使用TurboID进行邻近标记绘制口腔鳞状细胞癌预后相关蛋白NDRG1和PGK1的相互作用组图谱。

Mapping the Interactome of OSCC Prognostic-Associated Proteins NDRG1 and PGK1 Through Proximity Labeling Using TurboID.

作者信息

Câmara Guilherme A, Yokoo Sami, Granato Daniela C, Simabuco Fernando M, Ribeiro-Filho Helder V, Melo Reynaldo M, Pauletti Bianca A, Nascimento Filho Edson G, Domingues Romênia R, Paes Leme Adriana Franco

机构信息

Brazilian Biosciences National Laboratory - LNBio, Brazilian Center for Research in Energy and Materials - CNPEM, Campinas, São Paulo 13083-100, Brazil.

Department of Biochemistry, Federal University of São Paulo (UNIFESP), São Paulo 04021-001, Brazil.

出版信息

J Proteome Res. 2025 Jun 6;24(6):2741-2756. doi: 10.1021/acs.jproteome.4c01039. Epub 2025 Apr 30.

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck cancer, comprising over 90% of all oral malignancies worldwide. The identification of diagnostic and prognostic markers for OSCC is crucial for improving patient outcomes, as early detection and treatment are critical for the successful management of this disease. Previously, we demonstrated that (NDRG1) and (PGK1) are prognostic markers for OSCC; however, their role in OSCC development remains unclear. To investigate this, we used TurboID-based proximity labeling to identify the interactomes of NDRG1 and PGK1 in HEK293 cells. Herein, protein abundance patterns from three time points were used for clustering 364 proteins with a "fast" or "slow" response to biotin. Of these, 65 proteins were also identified in neoplastic islands of OSCC patients from our previous study, and 28 of these proteins have their gene expression associated with prognostic features, including death, metastasis, and relapse. PRM-MS enabled the quantification of 17 of these proteins, providing further evidence of their presence in the OSCC prognostic interactome. Finally, we characterized a prognostic-associated interactome composed of 28 proteins, which enabled the prioritization of candidates that can be further explored in OSCC progression. The mass spectrometry data generated in this study have been deposited in ProteomeXchange with the data set identifier PXD048046.

摘要

口腔鳞状细胞癌(OSCC)是一种常见的头颈癌类型,占全球所有口腔恶性肿瘤的90%以上。确定OSCC的诊断和预后标志物对于改善患者预后至关重要,因为早期检测和治疗对于成功管理这种疾病至关重要。此前,我们证明了(NDRG1)和(PGK1)是OSCC的预后标志物;然而,它们在OSCC发展中的作用仍不清楚。为了研究这一点,我们使用基于TurboID的邻近标记来鉴定HEK293细胞中NDRG1和PGK1的相互作用组。在此,来自三个时间点的蛋白质丰度模式用于对364种对生物素具有“快速”或“缓慢”反应的蛋白质进行聚类。其中,65种蛋白质也在我们之前研究的OSCC患者的肿瘤岛中被鉴定出来,其中28种蛋白质的基因表达与预后特征相关,包括死亡、转移和复发。PRM-MS能够对其中17种蛋白质进行定量,进一步证明了它们在OSCC预后相互作用组中的存在。最后,我们鉴定了一个由28种蛋白质组成的预后相关相互作用组,这使得能够对可在OSCC进展中进一步探索的候选物进行优先级排序。本研究中生成的质谱数据已存入ProteomeXchange,数据集标识符为PXD048046。

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