Non-melanoma skin cancers, including basal and squamous cell carcinomas (BCC and SCC), are the most common malignancies worldwide. BCC/SCC cancers are generally highly localized and can be surgically excised; however, invasive tumors may be fatal. Current diagnosis of skin cancer and prognosis of potential invasiveness are based mainly on clinical-pathological factors of the biopsied lesions. SCC invasiveness is also predicted by histomorphological factors, such as the degree of differentiation or the mitotic index, while BCCs are typically considered non-invasive. The above subjective measures do not provide direct, objective prognosis of cellular invasiveness in each specific sample. Hence, we have developed a mechanobiology-based approach to rapidly determine sample invasiveness. Here, cells from 15 fresh tissue samples of suspected non-melanoma skin cancer were seeded on physiological-stiffness (2.4 kPa) synthetic gels, and within 1-h invasive cell subsets were observed to push/indent the gel surface; clinicopathological results were separately obtained using standard protocols. The percentage of indenting cells from invasive (26.2 ± 2.4%) and non-invasive (4.8 ± 0.5%) SCC samples differed significantly (p < 0.0001), with well-separated invasiveness cutoffs of, respectively, > 12% and < 5%. The mechanical invasiveness directly agrees with the SCC cell-differentiation state, where over 3.3-fold more (p < 0.0001) cells from moderately differentiated samples indent the gels as compared to well-differentiated cell samples. In BCCs, < 20% of cells typically indented, and a highly migratory, desmoplastic sample was identified with 46%. By providing rapid, quantitative, early prognosis of invasiveness and potential metastatic risk, our rapid technology may facilitate informed (bed-side) decision making and choice of disease-management protocols on the time-scale of the initial diagnosis and surgical excision.

非黑色素瘤皮肤癌，包括基底细胞癌和鳞状细胞癌（BCC 和 SCC），是全球最常见的恶性肿瘤。BCC/SCC 癌症通常高度局部化，可以通过手术切除；然而，侵袭性肿瘤可能是致命的。目前皮肤癌的诊断和潜在侵袭性的预后主要基于活检病变的临床病理因素。SCC 侵袭性也可以通过组织形态学因素预测，例如分化程度或有丝分裂指数，而 BCC 通常被认为是非侵袭性的。上述主观测量不能提供每个特定样本中细胞侵袭性的直接、客观预测。因此，我们开发了一种基于机械生物学的方法来快速确定样品的侵袭性。这里，将来自 15 个疑似非黑色素瘤皮肤癌的新鲜组织样本的细胞接种在生理刚度 (2.4 kPa) 合成凝胶上，并在 1 小时内观察到侵袭性细胞亚群推动/缩进凝胶表面；使用标准方案分别获得临床病理学结果。来自侵入性（26.2 ± 2.4%）和非侵入性（4.8 ± 0.5%）SCC 样本的缩进细胞百分比显着不同（p  < 0.0001)，具有良好分离的侵袭性截止值，分别为 > 12% 和 < 5%。 机械侵袭性与 SCC 细胞分化状态直接一致，与分化良好的细胞样品相比，来自中度分化样品的细胞在凝胶上缩进超过 3.3 倍 ( p < 0.0001)。在 BCC 中，< 20% 的细胞通常呈缩进状，46% 的细胞被鉴定为高度迁移的促纤维增生样本。通过提供对侵袭性和潜在转移风险的快速、定量、早期预后，我们的快速技术可以促进在初步诊断和手术切除的时间范围内做出知情的（床边）决策和疾病管理方案的选择。