Background: The lack of screening methods for LSCC is a critical issue, as treatment options and the treatment outcome greatly depend on the stage of LSCC at initial diagnosis. Therefore, the objective of this study was to identify potential exosomal serum biomarkers that can diagnose LSCC and distinguish between early- and late-stage disease. Methods: A multiplexed proteomic array was used to identify differentially expressed proteins in exosomes isolated from the serum samples of LSCC patients compared to the control group (septorhinoplasty, SRP). The most promising proteins for diagnosis and differentiation were calculated using biostatistical methods and were validated by immunohistochemistry (IHC), Western blots (WB), and ELISA. Results: Exosomal insulin-like growth factor binding protein 7 (IGFBP7) and Annexin A1 (ANXA1) were the most promising exosomal biomarkers for distinguishing between control and LSCC patients and also between different stages of LSCC (fold change up to 15.9,p< 0.001 for all). Conclusion: The identified proteins represent potentially novel non-invasive biomarkers. However, these results need to be validated in larger cohorts with a long-term follow-up. Exosomal biomarkers show a superior signal-to-noise ratio compared to whole serum and may therefore be an important tool for non-invasive biomarker profiling for laryngeal carcinoma in the future.
背景：喉鳞状细胞癌（LSCC）筛查方法的缺失是一个关键问题，因为治疗方案及治疗效果在很大程度上取决于初诊时的LSCC分期。因此，本研究旨在鉴定能够诊断LSCC并区分早期与晚期疾病的潜在外泌体血清生物标志物。方法：采用多重蛋白质组学阵列技术，对LSCC患者血清样本中分离的外泌体蛋白与对照组（鼻中隔成形术，SRP）进行差异表达分析。通过生物统计学方法计算最具诊断与鉴别价值的蛋白质，并采用免疫组织化学（IHC）、蛋白质印迹（WB）和酶联免疫吸附测定（ELISA）进行验证。结果：外泌体胰岛素样生长因子结合蛋白7（IGFBP7）和膜联蛋白A1（ANXA1）是区分对照组与LSCC患者以及LSCC不同分期的最具潜力的外泌体生物标志物（所有比较倍数变化最高达15.9，p<0.001）。结论：所鉴定的蛋白质可能成为新型无创生物标志物。然而，这些结果需要在更大规模队列和长期随访中进行验证。与全血清相比，外泌体生物标志物显示出更优的信噪比，因此未来可能成为喉癌无创生物标志物分析的重要工具。
Exosomal Serum Biomarkers as Predictors for Laryngeal Carcinoma
肿瘤(癌症)患者之家