Open Access

ARTICLE

Regulation of RNA methylation and immune infiltration patterns by m5C regulators in head and neck squamous cell carcinoma

SHIDA HOU^1,#, TIANJUN LAN^2,#, YAOCHENG YANG^3,#, PEISHENG LIANG¹, XIN LIU^4,5, JUNJIE WANG⁶, ZHIFENG CHEN⁷, RONGSHENG ZENG^1,*, ZIJING HUANG^8,*

1 Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510095, China
2 Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510010, China
3 Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, 410000, China
4 Department of Stomatology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China
5 Department of Stomatology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, 528308, China
6 Hospital of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China
7 Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
8 Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, 510280, China

* Corresponding Authors: RONGSHENG ZENG. Email: ; ZIJING HUANG. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Frontiers in cancer: tumor microenvironment)

BIOCELL 2023, 47(12), 2641-2660. https://doi.org/10.32604/biocell.2023.043291

Received 27 June 2023; Accepted 06 October 2023; Issue published 27 December 2023

Abstract

Background: 5-Methylcytosine (m5C) methylation contributes to the development and progression of various malignant tumors. This study aimed to explore the potential role of m5C methylation regulators (m5CMRs) in head and neck squamous cell carcinoma (HNSCC). Methods: The transcription data of HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Subsequently, the m5C patterns in HNSCC were evaluated based on 14 m5CMRs. Then, the m5Cscore was developed to quantify m5C patterns by using principal component analysis (PCA) algorithms. Two single-cell RNA sequencing datasets and various methods were employed to assess the prognostic value and sensitivity to immunotherapy. Finally, key prognostic m5CMRs were identified using univariate COX regression analysis, and their clinical significance was validated based on the Human Protein Atlas (HPA) database and by using immunohistochemistry. Results: Two distinct m5C clusters were identified. m5C cluster A is characterized by an immune-activated microenvironment and is associated with a favorable prognosis. Notable differences were observed in prognosis, immune infiltration, and immunotherapy response between the high- and low-m5Cscore groups. Patients in the high-m5Cscore group exhibited high TMB, which is correlated with poor prognosis. The m5Cscore of epithelial cells in HNSCC was higher than that in other cells. Key prognostic m5CMRs, including NSUN2, DNMT3B, ALKBH1, and Y-Box Binding Protein 1 (YBX1), were associated with poor prognosis. Conclusion: Our research indicates that in head and neck squamous cell carcinoma, the m5C modification profoundly affects the TME’s diversity and complexity, influencing prognosis and the success of immunotherapy. Targeting m5C regulatory elements may be a new method for enhancing the efficacy of immunotherapy in HNSCC.

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