恶性间皮瘤（MM）和腹膜假粘液瘤（PMP）的腹内传播在恶性细胞在上皮-间质（E/M）轴上重塑过程中激活的干性窗口方面的特征很少。为了深入了解这些罕见形式的腹膜转移 (PM) 中的干性特性及其预后意义，通过乙醛脱氢酶 1 (ALDH1) 分析了 55 名接受热腹腔化疗进行细胞减灭手术的患者的原发肿瘤培养物中的癌症干细胞 (CSC) ）和球体形成测定，以及表达一组可塑性相关基因以测量 E/M 转变 (EMT) 分数。还分析了肿瘤内异质性。结直肠癌 PM 样本也被纳入其中进行比较。使用主成分和聚类分析确认分子数据。使用 Kaplan-Meier 和 Cox 回归模型评估与生存的关联。乙酰水杨酸 (ASA)（一种干性调节剂）的活性在五种培养物中进行了测试。显着增加的 ALDH1bright 细胞数量可识别出高级 PMP，并可将两种形式的 PM 中的实性肿块与腹水/粘蛋白包埋的肿瘤细胞区分开来。在多变量模型中，上皮/早期杂交EMT评分以及与多能因子相关的早期杂交表达模式与早期腹膜进展显着相关（分别为p = .0343和p = .0339，对数秩检验）。 ASA 损害了所有五种培养物中的球状体形成并增加了顺铂敏感性。这些数据表明 CSC 亚群和混合 E/M 状态可能引导 MM 和 PMP 的腹膜传播。干性可以被用作有针对性的脆弱性，以提高化疗敏感性并改善患者的治疗结果。需要进行更多研究来确认这些初步数据。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Intrabdominal dissemination of malignant mesothelioma (MM) and pseudomyxoma peritonei (PMP) is poorly characterized with respect to the stemness window which malignant cells activate during their reshaping on the epithelial-mesenchymal (E/M) axis. To gain insights into stemness properties and their prognostic significance in these rarer forms of peritoneal metastases (PM), primary tumor cultures from 55 patients selected for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were analyzed for cancer stem cells (CSC) by aldehyde dehydrogenase 1 (ALDH1) and spheroid formation assays, and for expression of a set of plasticity-related genes to measure E/M transition (EMT) score. Intratumor heterogeneity was also analyzed. Samples from PM of colorectal cancer were included for comparison. Molecular data were confirmed using principal component and cluster analyses. Associations with survival were evaluated using Kaplan-Meier and Cox regression models. The activity of acetylsalicylic acid (ASA), a stemness modifier, was tested in five cultures. Significantly increased amounts of ALDH1bright-cells identified high-grade PMP, and discriminated solid masses from ascitic/mucin-embedded tumor cells in both forms of PM. Epithelial/early hybrid EMT scores and an early hybrid expression pattern correlated with pluripotency factors were significantly associated with early peritoneal progression (p = .0343 and p = .0339, respectively, log-rank test) in multivariable models. ASA impaired spheroid formation and increased cisplatin sensitivity in all five cultures. These data suggest that CSC subpopulations and hybrid E/M states may guide peritoneal spread of MM and PMP. Stemness could be exploited as targetable vulnerability to increase chemosensitivity and improve patient outcomes. Additional research is needed to confirm these preliminary data.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.