Integrating molecular and immune biomarkers for precision therapy in hepatitis B: Associated hepatocellular carcinoma

Table 1 Key biomarker domains and their putative clinical implications in hepatitis B virus-associated hepatocellular carcinoma treated with sintilimab + lenvatinib

Domain	Feature/marker	Direction associated with longer progression-free survival	Biologic/mechanistic implication	Putative clinical relevance
Molecular (long noncoding RNAs)	High LINC01554 expression	Favourable	Tumour-suppressive activity; restrains Wnt/β-catenin and phosphoinositide 3-kinase/protein kinase B pathways	Candidate biomarker for selecting patients likely to respond to PD-1/tyrosine kinase inhibitor combinations
Immune	High CD4+ central memory T-cell infiltration	Favourable	Preserved adaptive memory enabling sustained immune reactivation after PD-1 blockade	Supports durable anti-tumour immunity and prolonged disease control
Immune (B-cell axis)	Enrichment of B-cell subsets (pro-B, class-switched memory, plasma cells)	Observed in responders	Tertiary lymphoid structure-like microenvironment	May augment CD4+/CD8+ T-cell coordination and checkpoint efficacy
Genomic	CUX1 mutation	Unfavourable	Transcriptional dysregulation; possible link to genomic instability	Potential prognostic marker of poor outcome; needs independent validation
Genomic (DNA repair)	FANCD2 mutation	Enriched in non-responders	Defective DNA repair and replication stress	May signify intrinsic therapy resistance or need for alternative pathway targeting
Clinical/anatomical	Solitary tumour morphology	Favourable	Lower clonal heterogeneity and contained microenvironment	Higher likelihood of durable response and successful conversion to resection or ablation

PD-1: Programmed cell death protein 1.