Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Table 7 Prognostic and predictive value of tissue biomarkers evaluated in hepatocellular carcinoma

Ref.	Marker	Patient (n)	Origin of specimen	Method assay	Quantification	Marker level	Clinical impact
Mitsuhashi et al[108]	Ang2	46	Resected specimens	RT-PCR and IHC	Quantitative	High tumor Ang2/1 ratio	Tumor portal vein invasion
							Large tumor
							Increase MVD
							Poor OS
Zhang et al[109]		38	Resected specimens	RT-PCR	No	High tumor Ang2/1 ratio	Large tumor
							Portal vein invasion
							Metastasis
Torimura et al[110]		59	Resected specimens (19) and Biopsy (40)	RT-PCR and IHC	Semi-quantitative	High tumor Ang2	Poor differentiated tumor
Abou-Alfa et al[127]	pERK	33	Biopsy before sorafenib	IHC	Semi-quantitative	High tumor pERK	Better TTP
Ozenne et al[128]		20	Biopsy before sorafenib	IHC	Semi-quantitative	High tumor pERK	No impact
Hagiwara et al[131]	JNK	39	Biopsy before sorafenib	IHC and Western Blot	Quantitative	High JNK tumor	Lower ORR
							Poorer TTP
							Poorer OS
Peng et al[134]	pVEGFR-2	35	Resected specimen before sorafenib	RT-PCR and IHC	Semi-quantitative	Low tumor expression	Poorer OS
Poon et al[84]	VEGF	60	Resected specimen	IHC and ELISA	Semi-quantitative	High tumor expression	Advanced HCC stage

Ang2: Angiopoietin 2; ELISA: Enzyme-linked immunoadsorbent assay; IHC: Immunohistochemistry; JNK: C-Jun N-Terminal Kinase; MVD: Microvessel density; ORR: Objective response rate; OS: Overall survival; pERK: Phosphorylated extracellular signal regulated kinase; pVEGFR: Phosphorylated vascular endothelial growth factors receptor; RT-PCR: Real-time polymerase chain reaction; TTP: Time to progression.