由于治疗方案和治疗目标有限，口腔癌带来了重大的健康挑战。我们的目的是研究牙龈颊口腔鳞状细胞癌 (GB-OSCC) 肿瘤的侵袭性边缘，从基因和细胞类型在不同距离边缘内可能导致淋巴结转移的定位角度来研究。我们收集了 23 个患者的肿瘤组织。使用数字空间转录组学切除 GB-OSCC 样本进行基因表达谱分析。我们监测了肿瘤与其微环境 (TME) 之间不同距离处的差异基因表达，并进行了解痉研究和免疫组织化学来鉴定调节 TME 的细胞和基因。我们发现肿瘤-基质界面（距离达 200 µm）肿瘤和免疫细胞之间）是 GB-OSCC 疾病进展最活跃的区域。差异最大的顶端基因，如 FN1 和 COL5A1，位于边缘的基质末端，与细胞外基质 (ECM) 的富集和免疫抑制的微环境一起，与淋巴结转移相关。中间成纤维细胞、肌细胞和中性粒细胞在肿瘤末端富集，而癌症相关成纤维细胞（CAF）在基质末端富集。中间成纤维细胞转化为 CAF 并重新定位到相邻的基质末端，在那里它们参与 FN1 介导的 ECM 调节。我们在 GB-OSCC 中生成了肿瘤-基质界面的功能组织，并鉴定了有助于淋巴结转移的空间定位基因和疾病进展。现在可以挖掘我们的数据集来发现口腔癌中合适的分子靶标。© 2024。作者。

Oral cancer poses a significant health challenge due to limited treatment protocols and therapeutic targets. We aimed to investigate the invasive margins of gingivo-buccal oral squamous cell carcinoma (GB-OSCC) tumors in terms of the localization of genes and cell types within the margins at various distances that could lead to nodal metastasis.We collected tumor tissues from 23 resected GB-OSCC samples for gene expression profiling using digital spatial transcriptomics. We monitored differential gene expression at varying distances between the tumor and its microenvironvent (TME), and performed a deconvulation study and immunohistochemistry to identify the cells and genes regulating the TME.We found that the tumor-stromal interface (a distance up to 200 µm between tumor and immune cells) is the most active region for disease progression in GB-OSCC. The most differentially expressed apex genes, such as FN1 and COL5A1, were located at the stromal ends of the margins, and together with enrichment of the extracellular matrix (ECM) and an immune-suppressed microenvironment, were associated with lymph node metastasis. Intermediate fibroblasts, myocytes, and neutrophils were enriched at the tumor ends, while cancer-associated fibroblasts (CAFs) were enriched at the stromal ends. The intermediate fibroblasts transformed into CAFs and relocated to the adjacent stromal ends where they participated in FN1-mediated ECM modulation.We have generated a functional organization of the tumor-stromal interface in GB-OSCC and identified spatially located genes that contribute to nodal metastasis and disease progression. Our dataset might now be mined to discover suitable molecular targets in oral cancer.© 2024. The Author(s).