Gene expression analysis of organoid model of human esophageal squamous cell carcinomas (ESCCs)

Esophageal squamous cell carcinoma (ESCC) is a serious cancer with a poor prognosis and a high recurrence rate after chemotherapy, which is a major clinical challenge. To elucidate the molecular basis of chemotherapy (chemo)-resistance and develop methods to effectively eliminate chemo-resistant tumor clones, we established a cancer organoid model from 24 ESCC patients of various stages, ages, and treatments. These ESCCOs recapitulated most oncogenic mutations of primary ESCC tissues and had tumorigenic properties upon xenografting. Each organoid line differs in its responsiveness to 5-fluorouracil (5-FU) and cisplatin (CDDP), chemotherapeutic agents commonly used to treat ESCC patients, with 7 lines exhibiting potent chemo-resistance. Importantly, these chemo-resistant ESCCOs had enhanced expression of genes involved in antioxidant stress response pathways and increased chromatin accessibility of their genomic loci, compared to chemo-sensitive ESCCOs, and these genes became useful biomarkers that can stratify chemo-resistant ESCC in histopathological specimens.