The results revealed the interaction between KPNA2 and PLAG1 in vivo. Table 1 The clinico-pathological characteristics of patients according to nuclear enrichment of PLAG1 Variate PLAG1 ▲ P-value Negative Positive All cases 171 143   Age (year), ≤60:>60 132:39 113:30 0.785 Gender, male:female 149:22 128:15 0.599 Child-Pugh, A:B

155:16 130:13 0.680 HBs antigen, positive:negative 150:21 123:20 0.737 HBe antigen positive:negative 35:136 31:112 0.889 AFP (ug/L), >20:≤20 62: 109 54: 89 0.815 Tumor size (cm), >5:≤5 81:90 88:55 0.030* No. tumor, Solitary:Multiple 140:31 111:32 0.451 Edmondson Grade, I + II:III + IV 22:149 12:131 NVP-BKM120 mouse 0.274 Vascular invasion, Present:Absent 99:72 88:55 0.564 Micro-metastases, Present:Absent 123:48 107:36 0.610 ▲: PLAG1 status in tumoral tissues. *represents statistical significance. Figure 3 The representative staining of KPNA2 and PLAG1 in clinical samples included in TMA. IHC staining of four tumoral tissues (T) was shown to define four groups: KnPn, low KPNA2 and low PLAG1 enrichment in nucleus; KnPp, low KPNA2 and high PLAG1 enrichment in nucleus; KpPn, high KPNA2 and low PLAG1 enrichment in nucleus; KpPp, high KPNA2 and high PLAG1 enrichment in nucleus. One paired non-tumoral tissue (NT) was shown as control to tumoral tissues. Magnification scales Sotrastaurin price represent 100 μm. Table 2 The co-enrichment

of KPNA2 and PLAG1 in both tumoral (T) and non-tumoral (NT) tissues Staining PLAG1 KPNA2 Correlation not (PLAG1/KPNA2) T NT P-value ▲ T NT P-value ▲ T ※ NT ※ Positive 143 77 <0.001 152

11 <0.001 R=0.362 R=0.254 Negative 171 237 162 303 P-value <0.001 P-value <0.001 ▲Represent the comparison of PLAG1 or KPNA2 nuclear staining between T and NT tissues. ※Represent the correlation of PLAG1 and KPNA2 nuclear staining in T or NT tissues. The tumoral PLAG1 expression correlates with survival of HCC patients Previous report has indicated the clinical significance of positive KPNA2 in tumoral tissue as prognostic predictor. Consistently, we determined that HCC patients with positive KPNA2 expression in tumoral tissue would develop more frequent recurrence and death (Figure 4a-b). Given that PLAG1 is an indispensable mediator for the function of KPNA2 in HCC cells, we hypothesized that nucleus enrichment of PLAG1 in tumoral tissue might be a malignant character of HCC. Through analysis of the association between the PLAG1 expression and clinic-pathological characteristics, we determined that the positive PLAG1 expression was associated with larger tumor size (Table 1, P = 0.030). We then examined whether positive PLAG1 expression level correlated with outcome of HCC patients after hepatectomy. We found that patients with positive PLAG1 expression would have poorer prognosis including recurrence free survival (RFS, Figure 4c) and overall survival (OS, Figure 4d) of HCC patients after hepatectomy.