Comprehensive Integrated Single-Cell Whole Transcriptome Analysis Revealed the p-EMT Tumor Cells—CAFs Communication in Oral Squamous Cell Carcinoma

Abstract

Cancer-associated fibroblasts (CAFs) and partial epithelial–mesenchymal transition (p-EMT) tumor cells are closed together and contribute to the tumor progression of oral squamous cell carcinoma (OSCC). In the present study, we deeply analyzed and integrated OSCC single-cell RNA sequencing datasets to define OSCC CAFs and p-EMT subpopulations. We highlighted the cell–cell interaction network of CAFs and p-EMT tumor cells and suggested biomarkers for the diagnosis and prognosis of OSCC during the metastasis condition. The analysis discovered four subtypes of CAFs: one p-EMT tumor cell population, and cycling tumor cells as well as TNFSF12-TNFRSF25/TNFRSF12A interactions between CAFs and p-EMT tumor cells during tumor metastasis. This suggests the prediction of therapeutically targetable checkpoint receptor–ligand interactions between CAFs and p-EMT tumor cells in OSCC regarding the metastasis status.

Single‐cell RNA sequencing reveals the heterogeneity of epithelial cell and fibroblast cells from non‐ to metastatic lymph node OTSCC

“…In our work, fibroblast cells were identified as CAFs by their high expression of the EMP3 and VIM, which is associated with carcinogenesis. This finding aligns with previous research 27 . The expression of EMP3 and VIM was confirmed in all subsets of fibroblast cells, which were subsequently categorized into nine distinct subclusters based on their differential gene expression profiles.…”

“…Fibroblast cells are indicated by the expression of DCN, myeloid cells by CD14 and CD168, endothelial cells by PECAM1 and TM4SF1, myofibroblast cells by MYL9, T cells by CD3E and CD3D, B cells by CD79A and MS4A1), and plasma cells by IGHG1 (Figure S1A). 27 The cell count was documented in Table S2. The cellular composition of all the specimens displayed a diverse tumor microenvironment, as illustrated in Figure 1C,D.…”

“…This finding aligns with previous research. 27 The expression of EMP3 and VIM was confirmed in all subsets of fibroblast cells, which were subsequently categorized into nine distinct subclusters based on their differential gene expression profiles. In accordance with the findings of the preceding investigation, our study also identified and differentiated the widely recognized classifications of iCAFs, myCAFs, and cCAFs through the use of biomarkers such as CXCL2, IL2, ACTC1, TNNT2, STMN1, among others.…”

“…A total of eight primary cell types were identified, which have been previously validated in both human and animal samples. 14,27 The primary populations consisted of both immune cells and non-immune cells, which encompassed cancer-associated cells that exhibited similarities to the HNSCC data. 40,41 The focus of our study was on the subpopulation, gene phenotype, and cell contact of fibroblast and epithelial cells in non-to metastasis OTSCC, given their prominent makeup in this context.…”

Activated fibroblasts induce immune escape of TSCC through CCL25/AKT pathway

“…Pelon et al (2020) confirmed that S1 CAFs promoted the migration and epithelial‐mesenchymal transition (EMT) of breast cancer cells via C‐X‐C motif chemokine ligand 12 (CXCL12) and transforming growth factor beta (TGF‐β) signaling, and the S4 subtype enhanced the invasion of cancer cells via NOTCH signaling. Recently, Huynh et al (2022) analyzed single‐cell sequencing data discovered four subtypes of CAFs: one p‐EMT tumor cell population, and cycling tumor cells as well as TNFSF12‐TNFRSF25/TNFRSF12A interactions between CAFs and p‐EMT tumor cells during tumor metastasis. Liu et al (2019) showed these cells mediate the immunosuppressive TME by promoting monocyte recruitment and macrophage differentiation (innate immunomodulatory functions) or modulating CD8 T‐cell function and differentiation (adaptive immune response).…”