Characterization of stem cell subtypes and prognostic signature in hepatocellular carcinoma

• Published in: Journal of cancer research and clinical oncology 2023-11, Vol.149 (15), p.14081-14100
• Main Authors: Qiu, Chenjie, Wu, Huili, Shi, Wenxiang
• Format: Article
• Language: English
• Subjects: Cancer Research; Chemotherapy; Hematology; Hepatocellular carcinoma; Immunology; Immunotherapy; Internal Medicine; Liver cancer; Medical prognosis; Medicine; Medicine & Public Health; Metabolism; Metastases; Mutation; Nomograms; Oncology; Patients; Prognosis; Risk groups; Stem cells
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-023-05239-3

Background Cancer stem cells (CSCs) were linked to cancer aggressiveness and poor prognosis in patients with hepatocellular carcinoma (HCC). Methods 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. Results 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. Conclusions 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.