异质性的存在使癌症治疗陷入了充满挑战的困境。我们通过单细胞测序 (scRNA-seq) 分析对 5 名胃腺癌患者的恶性上皮细胞进行了分析，证明了胃腺癌 (GA) 的异质性，并鉴定了与分化差和预后较差相关的 CCKBR 干细胞样癌细胞。我们进一步利用单细胞转录组文库（包括 40 个样本）进行了针对性分析，以证实这些筛选结果。此外，我们还发现FOXOs参与CCKBR胃腺癌的进展和发展。抑制 FOXO 的表达并破坏癌细胞干性，可减少 CCKBR GA 类器官的形成并阻止肿瘤进展。机械地、切割

The existence of heterogeneity has plunged cancer treatment into a challenging dilemma. We profiled malignant epithelial cells from 5 gastric adenocarcinoma patients through single-cell sequencing (scRNA-seq) analysis, demonstrating the heterogeneity of gastric adenocarcinoma (GA), and identified the CCKBR+ stem cell-like cancer cells associated poorly differentiated and worse prognosis. We further conducted targeted analysis using single-cell transcriptome libraries, including 40 samples, to confirm these screening results. In addition, we revealed that FOXOs are involved in the progression and development of CCKBR+ gastric adenocarcinoma. Inhibited the expression of FOXOs and disrupting cancer cell stemness reduce the CCKBR+ GA organoid formation and impede tumor progression. Mechanically, CUT&Tag sequencing and Lectin pulldown revealed that FOXOs can activate ST3GAL3/4/5 as well as ST6GALNAC6, promoting elevated sialyation levels in CCKBR+ tumor cells. This FOXO-sialyltransferase axis contributes to the maintenance of homeostasis and the growth of CCKBR+ tumor cells. This insight provides novel perspectives for developing targeted therapeutic strategies aimed at the treating CCKBR associated gastric cancer.© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.