Page 330 - Read Online

Page 6 of 10 Yao et al. Hepatoma Res 2018;4:30 I http://dx.doi.org/10.20517/2394-5079.2018.32

A Kaplan-Meier survival estimates, by Wnt5a B Kaplan-Meier survival estimates, by Wnt3a
1.0 1.0
High expression of Wnt5a Low or no expression
of Wnt3a
0.8 0.8

Cum survival 0.6 0.6

0.4
0.4
High expression of Wnt3a
Low or no expression of Wnt5a
0.2 0.2

0.0 0.0
0 20.0 40.0 60.0 0 20.0 40.0 60.0
Analysis time (month) Analysis time (month)

Figure 2. Overall survival curves of Wnt5a or Wnt3a expression in HCC [20,65] . The hepatic Wnt5a or Wnt3a expression curves were
calculated according to the Kaplan-Meier method. The accumulative survival curves of patients with HCC were made according to HCC
tissues with low or high expression for Wnt5a or Wnt3a level (log-rank test, P < 0.001). (A) Wnt5a in HCC; (B) Wnt3a in HCC. HCC:
hepatocellular carcinoma; Wnt3a: wingless-type MMTV integration site family member 3a; Wnt5a: wingless-type MMTV integration site
family member 5a

Table 2. Comparative analysis of circulating Wnt3a, AFP, HS-GGT, and GPC-3 detection in diagnosis of HCC
Wnt3a [19] AFP [19] HS-GGT [17] GPC-3 [67] Wnt3a [19]
(> 800 ng/L) (> 50 ng/mL) (> 5.5 U/L) (positive) + AFP
Sensitivity (%) 92.50 61.25 85.70 52.84 96.25
Specificity (%) 94.34 69.81 97.24 99.58 62.26
Accuracy (%) 93.23 64.66 96.20 83.57 82.71
PPV (%) 96.10 75.38 89.70 98.48 79.38
NPV (%) 89.29 54.41 92.23 80.20 91.67
Wnt3a + AFP: combining detection of serum Wnt3a and AFP concentration; Wnt3a (n = 80), AFP (n = 80), HS-GGT (n = 91), and
GPC-3 (n = 123). PPV: positive predictive value; NPV: negative predictive value; HCC: hepatocellular carcinoma; GPC-3: glypican-3; HS-
GGT: HCC-specific gamma-glutamyl transferase; AFP: alpha fetoprotein

provide greater chance for effective therapies or overcoming resistance to sorafenib . Many mechanisms
[76]
[75]
have been involved in the aberrant activation of Wnt signaling and regulating β-catenin activity or
[77]
function by using small molecules (LGK974 , Celecoxib , Genistein ), specific antibodies (OMP-54F28,
[80]
[79]
[78]
OTSA101) and small size peptide SAH-BCL-9 . However, only a few of anti-cancer drugs that have been
[82]
[81]
developed to target the related pathway of HCC formation or development have entered into pre-clinical
trials, and none of these have advanced to the late clinical trial stage.
Oncogenic Wnt3a is involved in HCC development and increasing Wnt3a plays a crucial role in cell
proliferation and metastasis, particularly in progression and mediated-oncogenesis involving signaling
pathways, with brown granule-like staining localized in cancerous parts of atypical hyperplasia [19,20] . Targeted
oncogenic glypican-3 gene transcription of Wnt upstream inhibited the proliferation of human hepatoma cells
by specific short hairpin RNA . Down-regulating Wnt3a expression inhibited cell viability and induced G0/G1
[83]
cell cycle arrest via decreased expression of cyclin D1 and c Myc, and increased expression of p21 and p27. In
addition, deletion of Wnt3a significantly inhibited migration and invasion by down-regulating MMP 2/-7/-9
expression via the MAPK (p38, ERK1/2 and JNK) pathway . The abnormality of liver and circulating Wnt3a
[61]
expression in HCC has provided initial evidence, and suggested that targeted-Wnt3a signaling could be a
promising target or an effective target for HCC therapy.