Integrated single-cell and bulk RNA sequencing analyses reveal a prognostic signature of cancer-associated fibroblasts in head and neck squamous cell carcinoma

Yichen Yang; Ben Ma; Litao Han; Weibo Xu; Xiaoxue Du; Wenjun Wei; Tian Liao; Qinghai Ji; Ning Qu; Yu Wang

doi:10.3389/fgene.2022.1028469

Integrated single-cell and bulk RNA sequencing analyses reveal a prognostic signature of cancer-associated fibroblasts in head and neck squamous cell carcinoma

Front Genet. 2022 Dec 8:13:1028469. doi: 10.3389/fgene.2022.1028469. eCollection 2022.

Authors

Yichen Yang^{1

2}, Ben Ma^{1

2}, Litao Han³, Weibo Xu¹, Xiaoxue Du^{1

2}, Wenjun Wei^{1

2}, Tian Liao^{1

2}, Qinghai Ji^{1

2}, Ning Qu^{1

2}, Yu Wang^{1

2}

Affiliations

¹ Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Otorhinolaryngology-Head and Neck Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Abstract

Objectives: To identify a prognosis-related subtype of cancer-associated fibroblasts (CAFs) in head and neck squamous cell carcinoma (HNSCC) and comprehend its contributions to molecular characteristics, immune characteristics, and their potential benefits in immunotherapy and chemotherapy for HNSCC. Materials and Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis of CAFs from the samples of HNSCC patients derived from Gene Expression Omnibus (GEO), to identify the prognosis-related subtype of CAFs. CAFs were clustered into five subtypes, and a prognosis-related subtype was identified. Univariate and multivariate cox regression analyses were performed on the cohort selected from The Cancer Genome Atlas (TCGA) to determine signature construction, which was validated in GSE65858 and GSE42743. A prognostic signature based on 4 genes was constructed, which were derived from prognosis-related CAFs. The molecular characteristics, immune characteristics as well as the predicted chemosensitivity and immunotherapeutic response in the signature-defined subgroups were analyzed subsequently. Results: The patients with higher CAF scores correlated with poor survival outcomes. Additionally, a high CAF score correlated with lower infiltration levels of many immune cells including M1 macrophages, CD8⁺ T cells, follicular T helper cells, monocytes, and naïve B cells. High CAF score also demonstrated different enrichment pathways, mutation genes and copy number variated genes. Furthermore, patients with high CAF scores showed lower sensitivity for chemotherapy and immunotherapy than those with low CAF scores. Conclusion: The results of our study indicate the potential of the CAF signature as a biomarker for the prognosis of HNSCC patients. Furthermore, the signature could be a prospective therapeutic target in HNSCC.

Keywords: bulk RNA sequencing; cancer-associated fibroblast; head and neck carcinoma; prognostic signature; single-cell sequencing.