Table 1.

Recent significant findings enhancing the understanding of heterogeneity in HCC.

Studies	Experimental techniques used	Findings/ Remarks
Xue et al. [91]	Exome and whole genome sequencing	Common mutations shared by all HCC lesions varied from 8% to 97%, indicating significant ITH. Confirmed correlation between the tumor size and ITH.
Ho et al. [92]	Single-cell RNA sequencing	A rare subpopulation of CD24+/CD44+ cells in HCC was identified, demonstrating the association of the CTSE gene in imparting stemness to HCC.
Ding et al. [93]	Next-generation sequencing and methylome analysis	Studied the genomic and epigenomic alterations and confirmed that various signaling pathways (JAK-STAT) and a combination of mutations (in TP53 and 17p) provide with HCC progression and replicative advantages.
Karagonlar et al. [40]	HuH-7 cell lines	KLF-4 induces EpCAM+/CD133+ LCSCs and modulates de-differentiation
Sun et al. [84]	Single-cell RNA sequencing	CCL5 chemokine is associated with immune evasion (by recruiting Tregs) in HCC and is overexpressed in circulating tumor cells
Yao et al. [94]	Single-cell RNA sequencing	AURKA and EZH2 expression contributes to tumor proliferation, HCC migration, and invasion.
Zhao et al. [95–100]	Spatial transcriptomics	Defined 6 marker genes as the prognostic signature in HCC. Tumors with histological similarities showed significant differences in transcription profiles.

CD Cluster of differentiation, CTSE Cathepsin E, JAK-STAT Janus kinase/signal transducers and activators of transcription, TP53 Tumor protein p53, KLF-4 Krüppel-like factor 4, EpCAM epithelial cell adhesion molecule, CCL5 C-C Motif Chemokine Ligand 5, Tregs Regulatory T cells, AURKA Aurora kinase A, EZH2 Enhancer of zeste homolog 2.