Prognostic biomarkers for prediction of recurrence of hepatocellular carcinoma: Current status and future prospects

Table 1 Gene expression studies of hepatocellular carcinoma for prediction of recurrence

Ref.	Sample type	Screening platform	Virus type	Characteristics for distinguishing groups	Number of marker genes	Predictive accuracy for recurrence
Iizuka et al[19] (2003)	Tumour tissues	Oligonucleotide microarray	HBV < HCV	Early IHR within 1 yr after surgery	12	25 in 27 independent patients (93%)
Kurokawa et al[20] (2004)	Tumour tissues	PCR based array	HBV < HCV	Early IHR within 2 yr after surgery	20	29 in 40 independent patients (72.5%)
Budhu et al[35] (2006)	Non-tumour tissues	cDNA microarray	Almost all HBV	Venous invasion or extrahepatic metastasis	17	87 of 95 independent patients (92%)
Ho et al[34] (2006)	Tumour tissues	cDNA microarray	HBV > HCV	Venous invasion	14	26 of 35 independent samples (74.3%)
Lee et al[37] (2006)	Tumour tissues	Oligonucleotide microarray	HBV > HCV	Hepatoblast gene signature	907	P < 0.001 in 66 patients (Probability of recurrence)
Okamoto et al[21] (2006)	Non-tumour tissues	cDNA microarray	All HCV	Single nodular HCC vs multicentric HCC	36	30 of 40 training samples (75%)
Wang et al[22] (2007)	Tumour tissues and non-tumour tissues	Oligonucleotide microarray	HBV > HCV	HCC recurrence	57	84% in 25 independent samples, sensitivity 86%, specificity 82%
Hoshida et al[23] (2008)	FFPE non-tumour tissues	DASL assay	HBV < HCV	Late recurrence more than 2 yr after resection	132	P = 0.003 in 224 patients in validation set (Probability of late recurrence)
Somura et al[24] (2008)	Tumour tissues	Oligonucleotide microarray/qRT-PCR	HBV < HCV	Early IHR within 1 yr after surgery	3	35 of 43 independent patients (81.4%)
Tanaka et al[25] (2008)	Tumour tissues	Oligonucleotide microarray	HBV > HCV	Aggressive recurrence exceeding Milan Criteria	1 (AURKB)	54 of 67 independent patients (80.5%)
Woo et al[26] (2008)	Tumour tissues	Oligonucleotide microarray	All HBV	Early IHR within 1 yr after surgery	628	P = 0.0018 in 139 independent patients (Probability of early recurrence)
Yoshioka et al[27] (2009)	Tumour tissues	Oligonucleotide microarray	HBV < HCV	Early IHR within 2 yr after surgery	172	P < 0.0001 in 97 independent patients (Probability of RFS)
Roessler et al[28] (2010)	Tumour tissues	Oligonucleotide microarray	HBV > HCV	Early IHR within 2 yr after surgery	161	P = 0.0057 for cohort 1, P = 0.017 for cohort 2 (Probability of RFS)
Tsuchiya et al[29] (2010)	Non-tumour tissues	Oligonucleotide microarray	All HCV	Late recurrence more than 1 yr after resection	38	P < 0.0001 in 44 training samples (Probability of RFS)
Woo et al[38] (2010)	Tumour tissues	Oligonucleotide microarray	HBV > HCV	Cholangiocarcinoma-like signature	625	P = 0.037 in cohort 1 of 61 patients, P = 0.004 for cohort 2 of 78 patients (Probability of RFS)
Weng et al[30] (2012)	Tumour tissues, PBMC	Oligonucleotide microarray	All HBV	Early IHR within 1 yr after surgery	3	P < 0.001 in 80 independent patients (Probability of RFS)
Xieraili et al[31] (2012)	Tumour tissues	Oligonucleotide microarray	HBV < HCV	Early IHR	1 (VIL1)	P = 0.025 in 90 independent patients (Probability of RFS)
Tsunedomi et al[32] (2013)	Tumour tissues	Oligonucleotide microarray	All HCV	Early IHR within 1 yr after surgery	1 (ABCB6)	89% sensitivity, 55% specificity, 86% PPV, 62% NPV in 20 independent patients

Under the heading “virus type”, HBV > HCV means that more patients in the study are HBV positive compared to HCV positive patients. HBV < HCV means there are more HCV positive patients in the study. DASL: Complementary cDNA-mediated annealing, selection, extension and ligation; IHR: Intrahepatic recurrence; RFS: Recurrence free survival; PBMC: Peripheral blood mononuclear cells; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma.