肝细胞癌中干细胞亚型的表征及预后标志物分析。
Characterization of stem cell subtypes and prognostic signature in hepatocellular carcinoma.
发表日期:2023 Aug 07
作者:
Chenjie Qiu, Huili Wu, Wenxiang Shi
来源:
Immunity & Ageing
摘要:
肿瘤干细胞(CSCs)与肝细胞癌(HCC)患者的肿瘤侵袭性和预后不良有关。我们整合两个外部HCC队列,根据未监督聚类和26个干细胞基因集开发了干细胞亚型。在亚型间,我们研究了预后、临床特征、已认知的HCC亚型、代谢特征、免疫相关特征、体细胞突变和药物敏感性的差异。我们创建了预后特征,并用多个队列进行验证,并将其用于评估免疫治疗和经导管动脉化疗栓塞(TACE)治疗的疗效。我们基于特征和临床特征开发了预后表。我们进一步研究了KIF20A在HCC中的功能,并通过蛋白质免疫印迹证实了KIF20A具有调控HCC细胞干性的潜力。低干细胞模式、良好预后、阳性临床特征、特定分子亚型、低转移特征和丰富的代谢和免疫方面与簇1相关,而簇2则相反。化疗和免疫治疗在簇1中更有效。簇1与CTNNB1和ALB突变更为密切相关。另外,高风险组的预后、免疫治疗和TACE治疗反应均较差。预后表可以预测HCC患者的生存概率。我们发现KIF20A在HCC中过表达,并与HepG2细胞系的干性相关联。我们确定了HCC患者中两个具有不同预后、代谢和免疫特征的干细胞亚群。我们还创建了基于7个基因的预后特征和预后表来估计生存概率。我们首次检查了KIF20A在HCC干性中的功能。© 2023. 本文作者(根据Springer Nature的独家许可)属于Springer-Verlag GmbH Germany的一部分。
Cancer stem cells (CSCs) were linked to cancer aggressiveness and poor prognosis in patients with hepatocellular carcinoma (HCC).We integrated two external HCC cohorts to develop the stem cell subtypes according to unsupervised clustering with 26 stem cell gene sets. Between the subtypes, differences in prognosis, clinical characteristics, recognized HCC subtypes, metabolic profile, immune-related features, somatic mutation, and drug sensitivity were examined. The prognostic signature was created, and validated by numerous cohorts, and used to assess the efficacy of immunotherapy and transcatheter arterial chemoembolization (TACE) treatment. The nomogram was developed based on the signature and clinical features. We further examined the function of KIF20A in HCC and proved that KIF20A had the potential to regulate the stemness of HCC cells through western blot.Low stem cell patterns, a good prognosis, positive clinical features, specific molecular subtypes, low metastatic characteristics, and an abundance of metabolic and immunological aspects were associated with Cluster 1, whereas Cluster 2 was the reverse. Chemotherapy and immunotherapy were more effective in Cluster 1. Cluster 1 and CTNNB1 and ALB mutation were more closely. Additionally, the prognosis, immunotherapeutic, and TACE therapy responses were all worse in the high-risk group. The nomogram could predict the survival probability of HCC patients. KIF20A was discovered to be overexpressed in HCC and was revealed to be connected to the stemness of the HepG2 cell line.Two stem cell subgroups with different prognoses, metabolic, and immunological characteristics in HCC patients were identified. We also created a 7-gene prognostic signature and a nomogram to estimate the survival probability. The function of KIF20A in HCC stemness was initially examined.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.