Int J Biol Sci 2021; 17(13):3476-3492. doi:10.7150/ijbs.61441 This issue

Research Paper

Multi-omics Analysis of Ferroptosis Regulation Patterns and Characterization of Tumor Microenvironment in Patients with Oral Squamous Cell Carcinoma

Wenchao Gu1, Mai Kim2, Lei Wang3,4, Zongcheng Yang5✉, Takahito Nakajima6✉, Yoshito Tsushima1

1. Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
2. Department of Oral and Maxillofacial Surgery, and Plastic Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan.
3. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
5. Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, People's Republic of China.
6. Department of Diagnostic and Interventional Radiology, University of Tsukuba, Ibaraki, Japan.

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Citation:
Gu W, Kim M, Wang L, Yang Z, Nakajima T, Tsushima Y. Multi-omics Analysis of Ferroptosis Regulation Patterns and Characterization of Tumor Microenvironment in Patients with Oral Squamous Cell Carcinoma. Int J Biol Sci 2021; 17(13):3476-3492. doi:10.7150/ijbs.61441. Available from https://www.ijbs.com/v17p3476.htm

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Abstract

Graphic abstract

Ferroptosis is a newly recognized mechanism of regulated cell death. It was reported to be highly associated with immune therapy and chemotherapy. However, its mechanism of regulation in the tumor microenvironment (TME) and influence on oral squamous cell carcinoma (OSCC) therapy are unknown. We identified a ferroptosis-specific gene-expression signature, an FPscore, developed by a principal component analysis (PCA) algorithm to evaluate the ferroptosis regulation patterns of individual tumor. Multi-omics analysis of ferroptosis regulation patterns was conducted. Three distinct ferroptosis regulation subtypes, which linked to outcomes and the clinical relevance of each patient, were established. A high FPscore of patients with OSCC was associated with a favorable prognosis, a ferroptosis-related immune-activation phenotype, potential sensitivities to the chemotherapy and immunotherapy. Importantly, a high FPscore correlated with a low gene copy number burden and high immune checkpoint expressions. We validated the prognostic value of the FPscore using independent immunotherapy and pan-cancer cohorts. Comprehensive evaluation of individual tumors with distinct ferroptosis regulation patterns provides new mechanistic insights, which may be clinically relevant for the application of combination therapies in OSCC.

Keywords: Ferroptosis, Oral squamous cell carcinoma, Prognosis, Tumor microenvironment, Immunotherapy