研究动态
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绘制唾液蛋白质组中可能与口腔癌侵袭性相关的构象变化。

Mapping Conformational Changes in the Saliva Proteome Potentially Associated with Oral Cancer Aggressiveness.

发表日期:2024 May 24
作者: Daniela C Granato, Carolina M Carnielli, Luciana D Trino, Ariane F Busso-Lopes, Guilherme A Câmara, Ana Gabriela C Normando, Helder V R Filho, Romênia R Domingues, Sami Yokoo, Bianca A Pauletti, Fabio M Patroni, Alan R Santos-Silva, Márcio A Lopes, Thaís Bianca Brandão, Ana Carolina Prado-Ribeiro, Paulo S Lopes-de Oliveira, Guilherme P Telles, Adriana F Paes Leme
来源: JOURNAL OF PROTEOME RESEARCH

摘要:

多种基于蛋白质组学的策略已应用于唾液,以定量识别口腔癌的诊断和预后目标。考虑到这些靶点可能受到并不意味着蛋白质丰度水平变化的事件的调节,我们假设蛋白质构象的变化可能与诊断和预后相关,揭示生物过程和临床相关的新靶点。为此,我们在唾液样本中采用有限蛋白水解质谱法来探索结构改变,比较健康对照和有或没有淋巴结转移的口腔鳞状细胞癌(OSCC)患者的蛋白质组。 36 种具有潜在结构重排的蛋白质与临床患者特征相关,包括转酮醇酶及其相互作用的伙伴。此外,N-糖基化肽有助于潜在诊断和预后标志物的结构重排。总而言之,这种方法利用唾液蛋白来寻找诊断和预测口腔癌的靶标,并可以指导发现蛋白质水平丰度之外的潜在调控位点。
Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.