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唾液蛋白质组学数据预测口腔癌生物标志物。

Prediction of Oral Cancer Biomarkers by Salivary Proteomics Data.

机构信息

Department of Science and High Technology, University of Insubria, 22100 Como, Italy.

Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy.

出版信息

Int J Mol Sci. 2024 Oct 16;25(20):11120. doi: 10.3390/ijms252011120.

Abstract

Oral cancer, representing 2-4% of all cancer cases, predominantly consists of Oral Squamous Cell Carcinoma (OSCC), which makes up 90% of oral malignancies. Early detection of OSCC is crucial, and identifying specific proteins in saliva as biomarkers could greatly improve early diagnosis. Here, we proposed a strategy to pinpoint candidate biomarkers. Starting from a list of salivary proteins detected in 10 OSCC patients and 20 healthy controls, we combined a univariate approach and a multivariate approach to select candidates. To reduce the number of proteins selected, a Protein-Protein Interaction network was built to consider only connected proteins. Then, an over-representation analysis (ORA) determined the enriched pathways. The network from 172 differentially abundant proteins highlighted 50 physically connected proteins, selecting relevant candidates for targeted experimental validations. Notably, proteins like Heat shock 70 kDa protein 1A/1B, Pyruvate kinase PKM, and Phosphoglycerate kinase 1 were suggested to be differentially regulated in OSCC patients, with implications for oral carcinogenesis and tumor growth. Additionally, the ORA revealed enrichment in immune system, complement, and coagulation pathways, all known to play roles in tumorigenesis and cancer progression. The employed method has successfully identified potential biomarkers for early diagnosis of OSCC using an accessible body fluid.

摘要

口腔癌占所有癌症病例的 2-4%,主要由口腔鳞状细胞癌(OSCC)组成,占口腔恶性肿瘤的 90%。OSCC 的早期检测至关重要,而将唾液中的特定蛋白质鉴定为生物标志物可以极大地提高早期诊断的准确性。在本研究中,我们提出了一种鉴定候选生物标志物的策略。首先,从 10 名 OSCC 患者和 20 名健康对照者的唾液蛋白检测列表中,我们结合了单变量和多变量方法来选择候选蛋白。为了减少选择的蛋白数量,我们构建了蛋白-蛋白相互作用网络,仅考虑相互连接的蛋白。然后,通过过表达分析(ORA)确定富集的通路。从 172 个差异丰度蛋白中构建的网络突出了 50 个具有物理连接的蛋白,这些蛋白为有针对性的实验验证选择了相关的候选蛋白。值得注意的是,在 OSCC 患者中,热休克 70kDa 蛋白 1A/1B、丙酮酸激酶 PKM 和磷酸甘油酸激酶 1 等蛋白被认为存在差异调节,这对口腔癌变和肿瘤生长具有重要意义。此外,ORA 揭示了免疫系统、补体和凝血途径的富集,这些途径都已知在肿瘤发生和癌症进展中发挥作用。本研究采用的方法成功地鉴定了用于 OSCC 早期诊断的潜在生物标志物,这些生物标志物可通过一种易于获取的体液进行检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a1/11508456/91c2e2cc868e/ijms-25-11120-g001.jpg

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