Abstract 5085: Network toxicology and single-cell RNA sequencing to reveal the mechanism of ethylene oxide inducing blood cancers

Abstract Introduction: During the COVID-19 pandemic, ethylene oxide (EO) was extensively utilized for mask disinfection to curb viral transmission. Despite its efficacy as a disinfectant, EO is a recognized carcinogen associated with an increased risk of leukemia and lymphoma. Understanding the carcinogenic dangers of EO exposure, especially in large-scale mask sterilization, is crucial for public health. Methods: This study investigated the molecular mechanisms linking EO exposure to the development of leukemia and lymphoma. We employed RNA sequencing data from The Cancer Genomes Atlas to construct prognostic models using LASSO Cox regression, Kaplan-Meier survival analysis, and multivariate survival regression. Key genes associated with each type of cancer were identified. Single-cell RNA sequencing was also utilized to examine gene expression within the tumor microenvironment. Enrichment analyses were conducted to identify the biological pathways involved, and cell-cell interactions, along with transcription factors, were analyzed to elucidate EO-induced oncogenic processes. Results: Our prognostic models identified two key genes for leukemia - ACKR3 and CCZ1B, and one for lymphoma - DECR2. Survival analysis revealed that high expression levels of ACKR3 (HR = 5.9, p = 1.5e-4) and CCZ1B (HR 0.15, p = 6.1e-5) are significantly associated with prognosis in leukemia patients. For lymphoma, DECR2 (HR = 19.85, p = 1.7e-4) similarly correlated with poorer survival rates. Single-cell RNA sequencing data demonstrated that ACKR3 and CCZ1B are predominantly expressed in monocytes/macrophages within the leukemia microenvironment, while DECR2 is highly expressed in advanced-stage lymphoma. Enrichment analyses indicated that apoptosis and cell cycle regulation pathways were significantly disrupted in both malignancies. Furthermore, critical cell-cell interactions involving ligand-receptor pairs (e.g., CXCL12-CXCR4) and transcription factors SPI1 (p = 0.001) and STAT1 (p = 0.003) were identified as potential mediators of EO-induced oncogenic processes. Conclusions: Prolonged EO exposure is associated with significant alterations in immune cell function and apoptotic mechanisms, thereby increasing the risk of developing leukemia and lymphoma. The identified prognostic genes and disrupted pathways provide insights into the molecular underpinnings of EO-induced carcinogenesis. These findings highlight the necessity for alternative disinfection methods and the implementation of stricter regulatory measures to mitigate the long-term carcinogenic risks posed by EO. Citation Format: Bitian Zhang, William C. Cho, Dongjie Wang. Network toxicology and single-cell RNA sequencing to reveal the mechanism of ethylene oxide inducing blood cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5085.