Stemness Landscape and Its Clinical Implications in Hepatocellular Carcinoma

Abstract

Abstract Background: It is generally accepted that hepatocarcinoma(HCC) originates from cancer stem cells (CSCs), which are responsible for HCC progression, metastasis and therapy resistance. The high heterogeneity of CSCs has precluded clinical application of CSC-targeting therapy. Here, we aimed to characterize the stemness landscapes and screen for certain patients more responsive to immunotherapy. Methods: Our study characterized two stemness-related subtypes with different prognosis and TME patterns in HCC patients, and constructed a 4-gene stemness-risk model through extensive bioinformatics analysis. We believe that our stem cell model has prospective clinical implications for prognostic assessment and may help physicians select prospective responders to prioritize the use of current immune checkpoint inhibitors. Results: Based on single-sample gene set enrichment analysis (ssGSEA) enrichments scores, HCC patients were classified into two subtypes (C1 and C2). The KM survival curve showed that C2 cluster had longer survival and better prognosis than C1 cluster. C2 had more significant Mast cell infiltration than C1. However, the infiltration of T cells CD4 memory resting\Dendritic cells\T cell regulatory (Tregs) was more pronounced in C1 than in C2. Patients in C2 had higher response rates to immunotherapy and were more likely to benefit from immunotherapy. C1 has a higher probability of immune escape than C2. Conclusion: Our study highlights the importance of precise molecular subtyping of stemness in HCC. The identification of two distinct stem cell subtypes, C1 and C2, provides valuable insights into the clinical heterogeneity of HCC and its correlation with prognosis, TME characteristics, and immunotherapy response rates.