Barra Leonarda, Carestia Elena, Ferri Giulia, Kazemi Mohammad, Ramahi Massoumeh, Priyadarshi Uditanshu, Di Resta Velia, Di Giuseppe Fabrizio, Ciccarelli Renata, Lococo Achille, Angelucci Stefania
General and Thoracic Surgery Unit-Casa di Cura Synergo-Pierangeli, Piazza L. Pierangeli 1, 65100 Pescara, Italy.
Center for Advanced Studies and Technologies (CAST), 'G d'Annunzio' University of Chieti-Pescara, Via 9, Luigi Polacchi 13, 66100 Chieti, Italy.
Int J Mol Sci. 2025 Aug 16;26(16):7924. doi: 10.3390/ijms26167924.
Early diagnosis of lung cancer, essential for reducing its high mortality rate, is currently challenging, partly due to the lack of specific biomarkers. Here, we attempted to develop a noninvasive and potentially sensitive screening method based on the proteomic analysis of unstimulated and stimulated saliva samples, collected by passive drooling and salivary swabs, respectively, from healthy heavy smokers enrolled in a nonprofit screening project. Protein content analyzed before and after sample cryopreservation for various periods and the associated two-dimensional electrophoresis revealed that protein extraction after short-term cryopreservation prevented the loss of detectable proteins. Mass spectrometric analysis of these electrophoretically resolved proteins revealed the presence of salivary proteins whose levels may be dysregulated in various types of lung cancer. Finally, in pilot experiments conducted on stimulated saliva from a patient with a lung cancer nodule, we detected altered content or selective presence of proteins involved in lung carcinogenesis, such as serpin B3 or the proteins S100A14 and aldoketoreductase-A1, respectively. While acknowledging that these findings require further validation, we believe that the use of saliva and related proteomic analyses may contribute to the identification of potential early lung cancer biomarkers, which could hopefully improve clinical management of the tumor and patient survival.
肺癌的早期诊断对于降低其高死亡率至关重要，但目前仍具有挑战性，部分原因是缺乏特异性生物标志物。在此，我们尝试基于对未刺激和刺激唾液样本的蛋白质组学分析开发一种非侵入性且可能敏感的筛查方法，这些样本分别通过被动流涎和唾液拭子从参与一个非营利性筛查项目的健康重度吸烟者中收集。对样本在不同时间段冷冻保存前后的蛋白质含量分析以及相关的二维电泳显示，短期冷冻保存后进行蛋白质提取可防止可检测蛋白质的损失。对这些经电泳分离的蛋白质进行质谱分析，发现存在唾液蛋白质，其水平在各种类型的肺癌中可能失调。最后，在对一名患有肺癌结节患者的刺激唾液进行的初步实验中，我们分别检测到参与肺癌发生的蛋白质含量改变或选择性存在，如丝氨酸蛋白酶抑制剂B3或蛋白质S100A14和醛糖酮还原酶 - A1。尽管认识到这些发现需要进一步验证，但我们相信唾液的使用及相关蛋白质组学分析可能有助于识别潜在的早期肺癌生物标志物，有望改善肿瘤的临床管理和患者生存率。
