了解头颈鳞状细胞癌（HNSCC）的侵袭和转移机制对于有效治疗至关重要，特别是在转移性病例中。在这项研究中，我们分析了来自 702,446 个细胞的多中心批量测序和综合单细胞数据，从而鉴定出一种新型癌症相关成纤维细胞 (CAF) 亚型，称为分泌型卷曲相关蛋白 2 CAF (SFRP2_CAF)。这些细胞源自平滑肌细胞，表现出类似于肌成纤维细胞 CAF 和炎症 CAF 的独特特征，并且与 HNSCC 患者较差的生存结果相关。我们的研究结果揭示了 SFRP2_CAF 和 SPP1 肿瘤相关巨噬细胞之间的显着相互作用，从而促进肿瘤侵袭和转移。此外，我们的研究通过基因调控网络分析和模拟扰动证实了核因子 I/X (NFIX) 是调节 SFRP2_CAFs 行为的关键转录因子。© 2024。作者。

Understanding the mechanisms of invasion and metastasis in head and neck squamous cell carcinoma (HNSCC) is crucial for effective treatment, particularly in metastatic cases. In this study, we analyzed multicenter bulk sequencing and comprehensive single-cell data from 702,446 cells, leading to the identification of a novel subtype of cancer-associated fibroblasts (CAFs), termed Secreted Frizzled-Related Protein2 CAFs (SFRP2_CAFs). These cells, originating from smooth muscle cells, display unique characteristics resembling both myofibroblastic CAFs and inflammatory CAFs, and are linked to poorer survival outcomes in HNSCC patients. Our findings reveal significant interactions between SFRP2_CAFs and SPP1 tumor-associated macrophages, which facilitate tumor invasion and metastasis. Moreover, our research identifies Nuclear factor I/X (NFIX) as a key transcription factor regulating SFRP2_CAFs behavior, confirmed through gene regulatory network analysis and simulation perturbation.© 2024. The Author(s).