Dataset Information

Single-cell RNA sequencing reveals pro-invasive cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma.

ABSTRACT:

Background

Hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among all head-and-neck cancers, and treatment options are limited. Tumor microenvironment (TME) analysis can help identify new therapeutic targets and combined treatment strategies.

Methods

Six primary HPSCC tissues and two adjacent normal mucosae from six treatment-naïve patients with HPSCC were analyzed using scRNA-seq. Cell types were curated in detail, ecosystemic landscapes were mapped, and cell-cell interactions were inferred. Key results were validated with The Cancer Genome Atlas and cell biology experiments.

Results

Malignant HPSCC epithelial cells showed significant intratumor heterogeneity. Different subtypes exhibited distinct histological features, biological behaviors, and spatial localization, all affecting treatment selection and prognosis. Extracellular matrix cancer-associated fibroblasts (mCAFs) expressing fibroblast activation protein were the dominant CAFs in HPSCC tumors. mCAFs, constituting an aggressive CAF subset, promoted tumor cell invasion, activated endothelial cells to trigger angiogenesis, and synergized with SPP1⁺ tumor associated macrophages to induce tumor progression, ultimately decreasing the overall survival of patients with HPSCC. Moreover, the LAMP3⁺ dendritic cell subset was identified in HPSCC and formed an immunosuppressive TME by recruiting Tregs and suppressing CD8+ T cell function.

Conclusions

mCAFs, acting as the communication center of the HPSCC TME, enhance the invasion ability of HPSCC cells, mobilizing surrounding cells to construct a tumor-favorable microenvironment. Inhibiting mCAF activation offers a new anti-HPSCC therapeutic strategy. Video Abstract.

SUBMITTER: Cai Z

PROVIDER: S-EPMC10585865 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Single-cell RNA sequencing reveals pro-invasive cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma.

Cai Zhimou Z Chen Lin L Chen Siyu S Fang Ruihua R Chen Xiaolin X Lei Wenbin W

Cell communication and signaling : CCS 20231018 1

<h4>Background</h4>Hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among all head-and-neck cancers, and treatment options are limited. Tumor microenvironment (TME) analysis can help identify new therapeutic targets and combined treatment strategies.<h4>Methods</h4>Six primary HPSCC tissues and two adjacent normal mucosae from six treatment-naïve patients with HPSCC were analyzed using scRNA-seq. Cell types were curated in detail, ecosystemic landscapes were mapped, and cel ...[more]

PMID: 37853464

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Project description:ObjectiveThe aim of this study was to construct a prognostic model based on the TP53 mutation to calculate prognostic risk scores of patients with HPSCC.MethodsTP53 mutation and transcriptome data were downloaded from the TCGA databases. Gene expression data from GSE65858, GSE41613, GSE3292, GSE31056, GSE39366, and GSE227156 datasets were downloaded from the GEO database. GSEA, univariate, multivariate Cox analyses, and LASSO analysis were employed to identify key genes and construct the prognostic model. ROC curves were utilized to validate the OS and RFS results obtained from the model. The associations between risk scores with various clinicopathological characteristics and immune scores were analyzed via ggplot2, corrplot package, and GSVA, respectively. Single-cell sequencing data was analyzed via unbiased clustering and SingleR cell annotations.ResultsInitially, two key genes, POLD2 and POLR2G, were identified and utilized to construct the prognostic model. Samples were divided into different risk groups via the risk scores obtained from the model, with high-risk group samples exhibiting poorer prognosis. Furthermore, the risk score exhibited a positive correlation with lymphatic metastasis in patients and the immune scores of CD4+ T, CD8+ T, dendritic cell, macrophage, and neutrophil. The immune responses also exhibited notable disparities between the high- and low-risk groups. The results of single-cell sequencing analysis demonstrated that epithelial cells and macrophages were relatively abundant in HPSCC samples. POLD2 and POLR2G exhibited higher expressions in epithelial cells, with most of the identified pathways also enriched in epithelial cells.ConclusionThe prognostic model exhibited a significant capacity for predicting the prognosis of HSPCC samples based on the TP53 mutation conditions and may also predict the cancer characteristics and immune infiltration scores of samples via different risk scores obtained from the model.Level of evidenceLevel 5.

Dataset Information

Single-cell RNA sequencing reveals pro-invasive cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma.

Background

Methods

Results

Conclusions

Publications

Single-cell RNA sequencing reveals pro-invasive cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma.

Similar Datasets

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