衰老相关分泌表型（SASP）与肝内胆管癌（ICC）的发生和进展密切相关。然而，其与 ICC 干性的关系仍不清楚。在该研究中，使用一类线性回归（OCLR）和单样本基因集富集分析（ssGSEA）算法计算ICC的干性指数。使用 ICC 的 Pearson 相关分析，总共鉴定了 14 个衰老相关干性基因 (SRSG)。随后，使用 ICC 共识聚类建立了 SRSG 相关分类。不同类型的 ICC 表现出不同的预后、免疫、代谢和致癌特征。此外，我们使用主成分分析 (PCA) 构建了 ICC 风险评分模型。风险评分与干性、免疫浸润、代谢和致癌特征呈正相关，但与 ICC 的预后呈负相关。高风险评分的患者可能对免疫治疗反应良好。此外，我们采用 3D 纤维蛋白凝胶来选择具有干性特征的肿瘤再生细胞 (TRC)。我们发现属于 14 个 SRSG 的 HELLS 在 ICC-TRC 中表达上调。沉默 HELLS 显着减少了 ICC-TRC 中的集落大小，抑制了迁移和侵袭，并减弱了 SASP。总之，我们为 ICC 提供了一种新颖的分类和风险评分，并揭示了 CSLC 可以获得活跃 SASP 的分子机制。© 2023 由 Elsevier B.V. 代表计算和结构生物技术研究网络出版。

The senescence-associated secretory phenotype (SASP) is closely associated with the tumorigenesis and progression of intrahepatic cholangiocarcinoma (ICC). However, it remains unclear its relation to stemness of ICC. In the study, the stemness indices of ICC were calculated using one-class linear regression (OCLR) and single-sample gene set enrichment analysis (ssGSEA) algorithms. A total of 14 senescence-related stemness genes (SRSGs) were identified using Pearson correlation analysis in ICC. Subsequently, a SRSGs-related classification was established using a consensus clustering for ICC. Different types of ICC exhibit distinct prognosis, immunity, metabolisms, and oncogenic signatures. Additionally, we constructed a risk score model for ICC using principal component analysis (PCA). The risk score was positively correlated with stemness, immune infiltration, metabolisms and oncogenic signatures, but negatively with prognosis in ICC. Patients with a high risk score may respond well to immunotherapy. Furthermore, we employed 3D fibrin gels to select tumor-repopulating cells (TRC) with stemness features. We found that HELLS, belonging to the 14 SRSGs, was up-regulated in ICC-TRC. And silencing HELLS significantly reduced the colony size, inhibited migration and invasion, and attenuated SASP in ICC-TRC. In summary, we provided a novel classification and risk score for ICC and uncovered a molecular mechanism via which CSLCs could obtain an active SASP.© 2023 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.