早期皮肤鳞状细胞癌（cSCC）的诊断在临床标准上往往具有挑战性，因为它可能与太阳性角化病（AK）或 Bowen 病（BD）呈相似症状，这些是 cSCC 的前体病变。目前，侵袭性活检的组织病理学评估是诊断的黄金标准。非侵入性诊断方法能够减轻患者和医疗系统的负担。因此，本研究使用带式剥取联合数据无关采集质谱（DIA-MS）蛋白质组学对组织病理学诊断的 AK、BD 和 cSCC 以及配对的正常样本进行了蛋白质组学分析，以确定在病变之间存在显著差异的蛋白质和生物功能。此外，采用支持向量机（SVM）机器学习算法评估了蛋白质组学数据在早期诊断 cSCC 中的可用性。研究共鉴定了 696 种蛋白质。使用蛋白质组学数据构建的机器学习模型能够以 77.5% 的准确率对前恶性病变（AK+BD）和恶性病变（cSCC）进行分类。差异丰度分析发现，在 cSCC 和 BD 样本中，共有 144 种和 21 种蛋白质组发生了显著变化，与正常皮肤相比（adj. p<0.05）。还观察到了癌变相关通路（如 LXR/RXR 激活、活性氧产生和 Hippo 信号通路）的变化，这可能解释了 cSCC 从前恶性病变进展的原因。总之，本研究表明，采用带式剥取样本的 DIA-MS 分析能够识别非侵入性蛋白质生物标志物，有潜力作为早期 cSCC 的补充诊断工具进行开发。© 2023 作者发表。由 John Wiley & Sons Ltd. 发表于《实验皮肤病学》。

Early cutaneous squamous cell carcinoma (cSCC) can be challenging to diagnose using clinical criteria as it could present similar to actinic keratosis (AK) or Bowen's disease (BD), precursors of cSCC. Currently, histopathological assessment of an invasive biopsy is the gold standard for diagnosis. A non-invasive diagnostic approach would reduce patient and health system burden. Therefore, this study used non-invasive sampling by tape-stripping coupled with data-independent acquisition mass spectrometry (DIA-MS) proteomics to profile the proteome of histopathologically diagnosed AK, BD and cSCC, as well as matched normal samples. Proteomic data were analysed to identify proteins and biological functions that are significantly different between lesions. Additionally, a support vector machine (SVM) machine learning algorithm was used to assess the usefulness of proteomic data for the early diagnosis of cSCC. A total of 696 proteins were identified across the samples studied. A machine learning model constructed using the proteomic data classified premalignant (AK + BD) and malignant (cSCC) lesions at 77.5% accuracy. Differential abundance analysis identified 144 and 21 protein groups that were significantly changed in the cSCC, and BD samples compared to the normal skin, respectively (adj. p < 0.05). Changes in pivotal carcinogenic pathways such as LXR/RXR activation, production of reactive oxygen species, and Hippo signalling were observed that may explain the progression of cSCC from premalignant lesions. In summary, this study demonstrates that DIA-MS analysis of tape-stripped samples can identify non-invasive protein biomarkers with the potential to be developed into a complementary diagnostic tool for early cSCC.© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.