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Liu et al. Novel predictive and prognostic strategies of HBV-related HCC

Table 1: Representative gene signature studies of hepatocellular carcinoma
Study Population Sample type Etiology Gene No. Different clinical outcomes
of subgroups
n = 61 (validation 1, Chinese)
Lee et al. [49] Tumor tissue HBV, HCV 907 Overall survival (P < 0.001)
n = 78 (validation 2, European)
Risk of survival/recurrence
n = 20 (training, Chinese)
Adjacent liver
Budhu et al. [50] HBV, 17 HR (95% CI) in validation set:
n = 95 (validation, Chinese) tissue
15.1 (5.0-45.8)/7.9 (2.5-25.0)
Kaposi-Novak et al. [51] n = 249 (Caucasian) Tumor tissue HBV, alcohol, 24 Overall survival (P < 0.001)
HCV
n = 23 (training, Asian) Rate of vascular invasion
Wang et al. [52] n = 25 (validation, Asian) Tumor tissue HBV, HCV 57 (accuracy: 84%; sensitivity: 86%;
specificity 82%)
Boyault et al. [53] n = 57 (training, French) Tumor tissue HBV, alcohol, 16 Overall survival (P < 0.001)
n = 63 (validation, French) HCV
Risk of early recurrence
Woo et al. [54] n = 65 (Chinese) Tumor tissue HBV 628 (within 2 years after surgery)
HR (95% CI):
12.539 (3.59-43.76)
Risk of late recurrence
n = 82 (training, Japanese) Adjacent liver (more than 2 years after surgery)
Hoshida et al. [55] HBV, HCV 132
n = 225 (validation, European) tissue HR (95% CI) in the validation set:
2.08 (1.03-4.18)
Coulouarn et al. [56] n = 139 (Caucasian) Tumor tissue HBV, alcohol, 249 Overall survival (P < 0.001)
HCV
Risk of early recurrence
Yoshioka et al. [57] n = 42 (training, Japanese) Tumor tissue HBV, HCV 172 (within 2 years after surgery)
n = 97 (validation, Japanese) HR (95% CI) in the validation set:
3.29 (1.83-5.91)
n = 61 (validation 1, Chinese) Risk of recurrence
Woo et al. [58] n = 78 (validation 2, Tumor tissue HBV, HCV 625 HR (95% CI) in the Chinese set:
Caucasian) 2.84 (1.51-5.34)
Risk of early recurrence
n = 247 (validation 1, Chinese) (within 2 years after surgery)
Roessler et al. [59] n = 139 (validation 2, GEO Tumor tissue HBV, HCV 161 HR (95% CI) in the Chinese set:
data)
2.72 (1.48-4.5)
Risk of recurrence
Tumor and 16 for tumor; HR (95% CI):
Villanueva et al. [60] n = 287 (Japanese) adjacent liver HBV, HCV 17 for adjacent 1.75 (1.20-2.53) for tumor signature;
tissue liver tissue 1.92 (1.20-3.06) for adjacent
signature
Risk of vascular invasion
HCV, HBV,
n = 79 (training, Caucasian)
Minguez et al. [61] Tumor tissues 35 HR (95 % CI) in the validation set
n = 135 (validation, Caucasian) alcohol
3.12 (1.29-7.51)
Risk of early recurrence
Weng et al. [62] n = 80 (Chinese) Tumor tissue HBV 3 (within 1 year after surgery)
HR (95% CI):
4.762 (1.764-12.856)
n = 139 (training, South Korea) Risk of poor survival
Kim et al. [63] n = 292 (validation, South Tumor tissue HBV 65 HR (95% CI) in validation the set:
Korea) 1.36 (1.13-1.64)
n = 56 (training, South Korea) Tumor and
Kim et al. [64] n = 40 (validation, South adjacent liver HBV 127 Overall survival (P < 0.001)
Korea) tissue
Risk of poor prognosis
Lim et al. [65] n = 286 (training, South Korea) Tumor tissue HBV 30 HR (95% CI) in validation set:
n = 83 (validation, China)
2.048 (1.130-3.712)
233 for late Risk of late recurrence
recurrence, HR (95% CI): 2.2 (1.3-3.7)
Kim et al. [66] n = 396 (Chinese) Tumor tissues HBV
65 for early Risk of early recurrence
recurrence HR (95% CI): 1.7 (1.1-2.6)
HBV: hepatitis B virus; HCV: hepatitis C virus; HR: hazard ratio; CI: confidence interval
basic patterns of HCC somatic mutations have been including TP53, TERT, CTNNB1, ARID1A, and AXIN1
extensively investigated. The somatic mutations are proved to be hotspots of genetic alteration [Table 2].
provide a novel genomic insight of molecular However, specific mutation in a single hot gene is not
classification and prognostic prediction. Some genes frequent, ranging from 5% to 20%. Such a low rate

Hepatoma Research ¦ Volume 2 ¦ December 23, 2016 335