Single-cell RNA sequencing reveals the heterogeneity of epithelial cell and fibroblast cells from non- to metastatic lymph node OTSCC,The FASEB Journal

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Single-cell RNA sequencing reveals the heterogeneity of epithelial cell and fibroblast cells from non- to metastatic lymph node OTSCC
The FASEB Journal ( IF 4.4 ) Pub Date : 2024-01-03 , DOI: 10.1096/fj.202301724r
Dandan Song ₁ , Fei Yang ₁ , Yang Sun ₁ , Xingwen Wu ₁ , Qianrong Zhou ₁ , Wei Bi ₁ , Jian Sun ₁ , Siyi Li ₂ , Youcheng Yu ₁

Affiliation

Lymph node metastasis (LNM) is one of the common features of oral tongue squamous cell carcinoma (OTSCC). LNM is also taken as a sign of advanced OTSCC and poor survival rate. Recently, single-cell RNA sequencing has been applied in investigating the heterogeneity of tumor microenvironment and discovering the potential biomarkers for helping the diagnosis and prognosticating. Pathogenesis of LNM in OTSCC remains unknown. Specifically, cancer-associated fibroblasts (CAFs) and epithelial tumor cells could foster the progression of tumors. Thus, in this study, we aimed to comprehensively analyze the roles of subpopulations of CAFs and epithelial tumor cells in lymph node metastatic OTSCC using the integration of OTSCC single-cell RNA sequencing datasets. Four distinct subtypes of CAFs, namely vascular CAFs, myofibroblast CAFs, inflammatory CAFs, and growth arrest CAFs were successfully discovered in LNM tumor and confirmed the roles of GAS and PTN pathways in the progression of tumor metastasis. In addition, NKAIN2+ epithelial cells and FN1+ epithelial cells specifically exhibited an upregulation of PTN, NRG, MIF, and SPP1 signaling pathways in the metastatic OTSCC. In doing so, we put forth some potential biomarkers that could be utilized for the purpose of diagnosing and prognosticating OTSCC during its metastatic phase and tried to confirm by immunofluorescence assays.

中文翻译：

单细胞 RNA 测序揭示非转移性淋巴结 OTSCC 上皮细胞和成纤维细胞的异质性

淋巴结转移（LNM）是口腔舌鳞状细胞癌（OTSCC）的常见特征之一。 LNM也被视为晚期OTSCC和生存率低的标志。近年来，单细胞RNA测序已被应用于研究肿瘤微环境的异质性并发现有助于诊断和预测的潜在生物标志物。 OTSCC LNM 的发病机制仍不清楚。具体来说，癌症相关成纤维细胞（CAF）和上皮肿瘤细胞可以促进肿瘤的进展。因此，在本研究中，我们旨在利用 OTSCC 单细胞 RNA 测序数据集的整合，全面分析 CAF 和上皮肿瘤细胞亚群在淋巴结转移性 OTSCC 中的作用。在LNM肿瘤中成功发现了四种不同的CAF亚型，即血管CAF、肌成纤维细胞CAF、炎症CAF和生长停滞CAF，并证实了GAS和PTN通路在肿瘤转移进展中的作用。此外，NKAIN2+上皮细胞和FN1+上皮细胞在转移性OTSCC中特别表现出PTN、NRG、MIF和SPP1信号通路的上调。在此过程中，我们提出了一些潜在的生物标志物，可用于诊断和预测 OTSCC 转移期的目的，并尝试通过免疫荧光测定进行确认。

更新日期：2024-01-04

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