Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

Table 2 Major molecular classifications of hepatocellular carcinoma

Ref.	Subclass	Marker	Main methods
Yamashita et al[158]	Type A-D	EpCAM, AFP	cDNA microarray, IHC
Lee et al[157,159]	Cluster A and B, and 3 distinct phenotypes	Sets of survival genes, AFP	Integrated cDNA microarray in human specimens and animal models
Boyault et al[160]	Groups G1-G6	Tumor heterozygosity, gene mutations, methylation, and HBV DNA	cDNA microarray, IHC, qRT-PCR
Hoshida et al[161]	Subclasses S1-S3	Cellular differentiation, serum AFP, signaling pathways	Meta-analysis of gene expression profiles datasets, IHC
Sia et al[163]	Immune classes active and adaptive	Immune response genes	cDNA microarray, IHC, TCGA analysis
Zhang et al[164]	Immunophenotypic subtypes 1-3	Immune response genes and antitumoral immunity	Whole-exome and RNA sequencing, mass spectrometry-based proteomics and metabolomics, CyTOF, single-cell analysis

HBV: Hepatitis B virus; IHC: Immunohistochemistry; TCGA: The Cancer Genome Atlas; AFP: Alpha-fetoprotein; qRT-PCR: Quantitative real-time polymerase chain reaction.