Photo Credit: Mohammed Haneefa Nizamudeen
The following is a summary of “Identification of molecular subtypes for integrated multi-omics analysis for use in guiding precision medicine in hepatocellular carcinoma,” published in the 2024 ASCO Annual Meeting under issue of Oncology by Chen et al.
Tumor microenvironment (TME) differences affect survival and treatment response in patients with hepatocellular carcinoma (HCC). Molecular subtypes help but have limitations in clinical use.
Researchers conducted a retrospective study to find better ways to handle TME diversity in HCC for improved prognosis and treatment response.
They combined three single-cell datasets from 39 patients to study the TME and found prognosis-related cell subclusters. Unsupervised clustering of subcluster-specific markers (SSMs) genes generated transcriptomic subtypes. The subtypes’ predictive value was explored in external HCC cohorts and a real-world cohort receiving immune checkpoint blockade (ICB) therapy. Cancer stemness was estimated using bioinformatic methods, and TME features were validated using various techniques like single-cell RNA-seq and immune repertoire sequencing, mass cytometry (CyTOF), and multiplex immunofluorescence (mIF). Finally, a prognosis-related score (PRS) and identified potential therapeutic targets were developed for patients with high PRS.
The results showed that single-cell analysis revealed TME diversity in HCC, identifying 6 prognostically relevant cell clusters. Five transcriptomic subtypes showed different clinical prognosis, stemness characteristics, immune profiles, and treatment responses. Class 1 had better outcomes, while classes 2 and 4 lacked T cell infiltration. Classes 5 and 3 were immune-suppressed and sensitive to ICB and targeted therapy, while classes 1 and 2 responded better to transcatheter arterial chemoembolization treatment (TACE). Class 4 was resistant to all HCC treatments. The PRS predicted prognosis well across cohorts of HCC, identifying potential therapeutic targets and agents for patients with high PRS.
Investigators concluded that the study produced a functional molecular classification for HCC, offering direction for precision medicine in patient care.
Source: meetings.asco.org/abstracts-presentations/233942
