HELLS modulates the stemness of intrahepatic cholangiocarcinoma through promoting senescence-associated secretory phenotype.
HELLS modulates the stemness of intrahepatic cholangiocarcinoma through promoting senescence-associated secretory phenotype.
复制标题
DOI：
10.1016/j.csbj.2023.09.020
复制
发表时间：
2023
影响因子：
6
通讯作者：
中科院分区：
文献类型：
--
作者：
衰老相关分泌表型（SASP）与肝内胆管细胞癌（ICC）的发生、发展密切相关。然而，它与国际刑事法院的独立性的关系仍然不清楚。在这项研究中，使用一类线性回归（Oscillation）和单样本基因集富集分析（ssGSEA）算法计算ICC的干性指数。通过Pearson相关分析，共鉴定出14个衰老相关的干性基因（SRSGs）。随后，使用ICC的共识聚类建立了与特别代表有关的分类。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，我们构建了一个风险评分模型，ICC使用主成分分析（PCA）。ICC的危险评分与干细胞、免疫浸润、代谢和致癌特征呈正相关，与预后呈负相关。具有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增殖细胞（TRC）。我们发现，属于14个SRSG的HELLS在ICC-TRC中上调。沉默HELLS基因可显著降低ICC-TRC中的殖民地大小，抑制SASP的迁移和侵袭。总之，我们为ICC提供了一种新的分类和风险评分，并揭示了CSLCs获得活性SASP的分子机制。我们在肝内胆管癌中发现了几个与衰老相关的干性基因。我们建立了一个新的肝内胆管细胞癌分类系统。我们建立了一个新的风险评分与预后标志的肝内胆管癌。HELLS通过刺激衰老相关分泌表型促进肝内胆管癌的干性。
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. We identified several senescence-related stemness genes in intrahepatic cholangiocarcinoma. We constructed a novel classification system for intrahepatic cholangiocarcinoma. We established a novel risk score with prognosis signature in intrahepatic cholangiocarcinoma. HELLS promoted the stemness of intrahepatic cholangiocarcinoma via stimulating senescence-associated secretory phenotype.
登录
查看更多内容
影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
64.5
作者：
Malta TM;Sokolov A;Gentles AJ;Burzykowski T;Poisson L;Weinstein JN;Kamińska B;Huelsken J;Omberg L;Gevaert O;Colaprico A;Czerwińska P;Mazurek S;Mishra L;Heyn H;Krasnitz A;Godwin AK;Lazar AJ;Cancer Genome Atlas Research Network;Stuart JM;Hoadley KA;Laird PW;Noushmehr H;Wiznerowicz M
通讯作者：
Wiznerowicz M
影响因子：
14.5
作者：
Chibaya, Loretah;Snyder, Jarin;Ruscetti, Marcus
通讯作者：
Ruscetti, Marcus
影响因子：
7.3
作者：
Lv, Yigang;Wu, Liyuan;Jian, Huan;Zhang, Chi;Lou, Yongfu;Kang, Yi;Hou, Mengfan;Li, Zhen;Li, Xueying;Sun, Baofa;Zhou, Hengxing
通讯作者：
Zhou, Hengxing