A novel molecular subtype identification applied to individualized treatment of mRNA vaccines for hepatocellular carcinoma

This study aims to identify potential tumor antigens in hepatocellular carcinoma (HCC). It further seeks to establish a genomic-based immunotyping classification for HCC and explore its clinical application value. Gene expression profiles and corresponding clinical data were obtained from the GEO and TCGA databases, respectively. The cBioPortal platform was utilized to visualize, compare, and identify key genetic alterations. Consensus clustering analysis was performed to determine immune subtypes, followed by comprehensive assessments of their prognostic significance, drug sensitivity, response to immunotherapy, expression levels of immune checkpoints and modulators, and immune marker profiles. An immune landscape was constructed based on the expression patterns of immune-related genes. Additionally, an immune gene co-expression network was established to explore gene distribution and enriched signaling pathways across distinct modules. The cBioPortal platform was utilized to screen 10 tumor-associated antigens: CLEC3B, EEF1E1, EIF25B, EIF5B, EZH2, GAS2L3, KIF2C, NABP2, NDC1, and SFPQ. Based on comprehensive profiling, HCC patients were classified into two distinct molecular subtypes (C1 and C2), each exhibiting unique molecular, cellular, and clinical features. Patients with the C1 subtype exhibited poorer overall survival compared to those with the C2 subtype. C1 subtype was characterized by elevated expression levels of immune checkpoint genes and immune cell markers. Weighted Gene Co-expression Network Analysis (WGCNA) revealed that the blue module displayed the strongest association with molecular subtypes and was significantly enriched in key signaling pathways, including MYC and NOTCH. Molecular typing of HCC can facilitate the prediction of patient prognosis. Patients with the C1 subtype exhibit poor prognostic outcomes, characterized by low immunogenicity and diminished anti-tumor immune activity. Consequently, these potential antigens demonstrate the most promising therapeutic efficacy in the C2 subtype.