Smoking-induced shifts in salivary exosomal cytokines and amino acid profiles as potential early biomarkers for oral cancer

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2025-01-11 DOI:10.1016/j.cyto.2025.156857

Afsareen Bano , Ravina Vats , Pooja Yadav , Mala Kamboj , Rashmi Bhardwaj

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Abstract

Background

Chronic smoking is an established risk factor for oral cancer (OC). The role of tobacco in oral squamous cell cancer (OSCC) emphasizes the need for non-invasive diagnostic approaches to identify early molecular alterations and improve patient outcomes. Salivary exosomes, which contain proteins, lipids, and nucleic acids, accessible and rich in biological content, making them interesting candidate biomarkers.

Methods

Saliva samples were collected from non-smokers (n = 20), smokers (n = 20), and patients with oral cancer (n = 20). Salivary exosomes were isolated and characterized using various techniques, including estimation of protein concentrations and amino acid profiling using High-Performance Liquid Chromatography (HPLC). Fourier Transform Infrared (FTIR) spectroscopy analyzed protein and amino acid peaks, while enzyme-linked immunosorbent assay (ELISA) measured pro-inflammatory cytokines IL-6 and IL-8.

Results

Elevated levels of salivary exosomal proteins (p = 0.017), IL-6 (p = 0.008), and IL-8 (p = 0.0004), along with significant alterations in amino acid profiles, were observed in smokers compared with non-smokers. Additionally, protein (p = 0.005) and IL-6 (p = 0.004) levels were significantly elevated in oral cancer compared to non-smoker group. FTIR spectroscopy revealed distinct molecular fingerprints in exosomes, highlighting changes in protein and amino acid concentrations and indicating altered metabolism.

Conclusion

This comparative cross-sectional study demonstrated that chronic smoking induces significant biochemical changes in salivary exosomes, establishing them as promising non-invasive biomarkers for early oral cancer detection. Elevated pro-inflammatory cytokines IL-6 and IL-8, along with altered amino acid profiles, may create pre-cancerous conditions. Notably, along with altered amino acid profiles, IL-6 levels progressively increase from smoking to oral cancer, highlighting its potential role in cancer progression.

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吸烟诱发的唾液外泌体细胞因子和氨基酸谱变化是潜在的口腔癌早期生物标志物。

背景：长期吸烟是口腔癌（OC）的一个确定的危险因素。烟草在口腔鳞状细胞癌（OSCC）中的作用强调了采用非侵入性诊断方法来识别早期分子改变和改善患者预后的必要性。唾液外泌体含有蛋白质、脂质和核酸，易于获取且具有丰富的生物学含量，使其成为有趣的候选生物标志物。方法：采集非吸烟者（n = 20）、吸烟者（n = 20）和口腔癌患者（n = 20）的唾液样本。唾液外泌体的分离和表征使用各种技术，包括估计蛋白质浓度和氨基酸分析使用高效液相色谱（HPLC）。傅里叶变换红外光谱（FTIR）分析蛋白质和氨基酸峰，酶联免疫吸附试验（ELISA）检测促炎细胞因子IL-6和IL-8。结果：吸烟者与非吸烟者相比，唾液外泌体蛋白（p = 0.017）、IL-6 （p = 0.008）和IL-8 （p = 0.0004）水平升高，氨基酸谱也有显著改变。此外，与非吸烟者相比，口腔癌患者的蛋白质（p = 0.005）和IL-6 （p = 0.004）水平显著升高。FTIR光谱显示外泌体中明显的分子指纹，突出显示蛋白质和氨基酸浓度的变化，表明代谢改变。结论：本比较横断面研究表明，慢性吸烟诱导唾液外泌体发生显著的生化变化，使其成为早期口腔癌检测的有前途的非侵入性生物标志物。促炎细胞因子IL-6和IL-8的升高，以及氨基酸谱的改变，可能导致癌前病变。值得注意的是，随着氨基酸谱的改变，IL-6水平从吸烟到口腔癌逐渐增加，突出了其在癌症进展中的潜在作用。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.