Multi-omics analysis deciphers intercellular communication regulating oxidative stress to promote oral squamous cell carcinoma progression

Hongrong Zhang; Yemei Qian; Yang Zhang; Xue Zhou; Shiying Shen; Jingyi Li; Zheyi Sun; Weihong Wang

doi:10.1038/s41698-024-00764-x

Multi-omics analysis deciphers intercellular communication regulating oxidative stress to promote oral squamous cell carcinoma progression

NPJ Precis Oncol. 2024 Nov 21;8(1):272. doi: 10.1038/s41698-024-00764-x.

Authors

Hongrong Zhang^#^{1

2}, Yemei Qian^#^{1

2}, Yang Zhang^#³, Xue Zhou¹, Shiying Shen^{1

2}, Jingyi Li¹, Zheyi Sun^{4

5}, Weihong Wang^{6

7}

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China.
² Yunnan Key Laboratory of Stomatology, Kunming, China.
³ Department of Vascular Surgery, Fuwai Yunnan Cardiovascular Hospital, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, China.
⁴ Yunnan Key Laboratory of Stomatology, Kunming, China. sunzheyi@kmmu.edu.cn.
⁵ Department of Endodontics, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China. sunzheyi@kmmu.edu.cn.
⁶ Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China. wangweihong@kmmu.edu.cn.
⁷ Yunnan Key Laboratory of Stomatology, Kunming, China. wangweihong@kmmu.edu.cn.

^# Contributed equally.

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck, associated with high recurrence and poor prognosis. We performed an integrated analysis of single-cell RNA and spatial transcriptomic data from cancerous and normal tissues to create a comprehensive atlas of epithelial cells and cancer-associated fibroblasts (CAFs). Our findings show that AKR1C3⁺ epithelial cells, located at the tumor's stromal front, exhibit significant copy number variation and poor prognostic indicators, suggesting a role in tumor invasion. We also identified a distinct group of early-stage CAFs (named OSCC_Normal, characterized by ADH1B⁺, MFAP4⁺, and PLA2G2A⁺) that interact with AKR1C3+ cells, where OSCC_Normal may inhibit the FOXO1 redox switch in these epithelial cells via the IGF1/IGF1R pathway, causing oxidative stress overload. Conversely, AKR1C3⁺ cells use ITGA6/ITGB4 receptor to counteract the effects of OSCC_Normal, promoting cancer invasion. This study unveils complex interactions within the OSCC tumor microenvironment.