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Single-cell transcriptome profiling of the stepwise progression of head and neck cancer

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) undergoes stepwise progression from normal tissue to metastasized tumors. To comprehensively delineate the heterogeneity of tumor cells and their interactions during the progression of HNSCC, we employed single-cell RNA-seq (scRNA-seq) profiling for the tissues of normal, leukoplakia, HNSCC, and metastasized HNSCC. We identified novel clones of malignant cells expressing LGALS7B and fibroblasts expressing CXCL8, and the abundance of these cells in the tumor tissue was associated with poorer prognostic outcomes. In addition, we demonstrated that fibroblasts in leukoplakia and tumor tissue express COL1A1, which interacts with CD44+ malignant cells, facilitating HNSCC progression. CD4+FOXP3+ regulatory T cells expand in leukoplakia and express LAIR2 with collagen stimulation, which may provide a favorable microenvironment for tumor progression. In conclusion, stromal and immune cell interactions play critical roles in the stepwise progression of HNSCC, and we have identified steps during HNSCC progression for possible therapeutic interventions

ORGANISM(S): Homo sapiens

PROVIDER: GSE181919 | GEO | 2022/08/31

REPOSITORIES: GEO

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Project description:To study of differential effect on cancer-associated fibroblasts of HNSCC, we have employed microarray expression profiling. The critical effect of the tumor microenvironment to caner progression is well recognized. Recent research suggests that the cancer-promoting properties of the tumor stroma may attributed to fibroblasts. However, little is known about fibroblasts that inhibit cancer progression. From the immunohistochemical analysis of cancer tissues from head and neck squamous cell carcinoma (HNSCC) patients, we divided cancer-associated fibroblast (CAF) into two groups depending on whether the boundary between epithelial cancer cells and the surrounding extracellular matrix (ECM) is clear and smooth or not. Therefore, we tried to evaluate whether there is a difference between these two CAFs in HNSCC progression. CAF was primary cultured, followed by co-culture with HNSCC cell to observe the effect on Matrigel invasion. The mRNA expression patterns between these two CAF groups were compared by DNA microarray analysis. FaDu cell and primary CAF from each group was co-transplanted into the oral mucosa of mice, and the tumorigenesis was compared. The CAF group (CAF-Promote, CAF-P) from cancer tissues which have unclear boundary between ECM and epithelial cancer cells showed a tendency to stimulate in vitro Matrigel invasion of HNSCC cell. On the contrary, the CAF group (CAF-Defense, CAF-D) from cancer tissues, which have clear boundary with epithelial cancer cell caused no remarkable increase of Matrigel invasion. In addition, CAF-D reduced the tumorigenicity of FaDu compared to CAF-P in the in vivo mice model. In DNA microarray analysis, COL3A1, COL6A6, COL25A1, and COL26A1 were particularly highly expressed in CAF-D group. In this study, these collagen proteins derived from cancer stroma were found to have a function of inhibiting the progression of HNSCC. It is expected to provide important information for predicting the prognosis of HNSCC and development of drug target in the future.

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Single-cell transcriptome profiling of the stepwise progression of head and neck cancer

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