Decrease of RBM4 indicates poor prognosis in patients with hepatocellular carcinoma after hepatectomy

Figures & data

Table 1 Association between RBM4 expression and clinicopathologic factors of 95 HCC patients

Clinicopathologic factors	N	RBM4 expression levels		P-value
		High	Low
Sex				0.552
Female	15	4 (26.7%)	11 (73.3%)
Male	80	20 (25.0%)	60 (75.0%)
Age (years)				0.126
≤60	72	16 (22.2%)	56 (77.8%)
>60	23	8 (34.8%)	15 (65.2%)
AFP (ng/mL)				0.109
≤20	34	11 (32.4%)	23 (67.6%)
>20	61	13 (21.3%)	48 (78.7%)
Hepatitis B status				0.039
Positive	75	13 (17.3%)	62 (82.7%)
Negative	20	11 (55.0%)	9 (45.0%)
Liver cirrhosis				0.033
Presence	61	7 (11.5%)	54 (88.5%)
Absence	34	17 (50.0%)	17 (50.0%)
Child–Pugh classification				0.098
A	84	19 (22.6%)	65 (77.4%)
B	11	5 (45.5%)	6 (54.5%)
Tumor number				0.047
Solitary	42	17 (40.5%)	25 (59.5%)
Multiple	53	7 (13.2%)	46 (86.8%)
Tumor size				0.110
≤5 cm	33	13 (39.4%)	20 (60.6%)
>5 cm	62	11 (17.7%)	51 (82.3%)
Capsular formation				0.041
Presence	35	17 (48.6%)	18 (51.4%)
Absence	60	7 (11.7%)	53 (88.3%)
Vascular invasion				0.003
Presence	25	15 (60.0%)	10 (40.0%)
Absence	70	9 (12.9%)	61 (87.1%)
Edmondson–Steiner grade				0.815
Low grade (I and II)	49	13 (26.5%)	36 (73.5%)
High grade (III and IV)	46	11 (23.9%)	35 (76.1%)
UICC/AJCC stage				0.046
I	41	18 (43.9%)	23 (56.1%)
II–III	54	6 (11.1%)	48 (88.9%)
BCLC stage				0.001
0–A	32	18 (56.3%)	14 (43.7%)
B–C	63	6 (9.5%)	57 (90.5%)

Note: Bold figures represent P<0.05.

Abbreviations: RBM4, RNA-binding motif 4; HCC, hepatocellular carcinoma; AFP, alpha feto protein; BCLC, Barcelona clinic liver cancer; UICC, Union for International Cancer Control; AJCC, American Joint Committee on Cancer.

Figure 1 Immunohistochemistry of RBM4 expression in HCC tissues.

Notes: In these representative images, the percentage of positive RBM4 expression hepatocytes was more than 50% (scored as 3, A), the percentage of positive RBM4 expression hepatocytes was 25%–50% (scored as 2, B), the percentage of positive RBM4 expression hepatocytes was 10%–25% (scored as 1, C), the percentage of positive RBM4 expression hepatocytes was not more than 10% (scored as 0, D); original magnification ×400.
Abbreviations: RBM4, RNA-binding motif 4; HCC, hepatocellular carcinoma.

Figure 2 Correlations of RBM4 expression with the overall survival and disease-free survival of HCC.

Notes: (A) Overall survival was analyzed according to the expression of RBM4 in 95 cases of HCCs (the Kaplan–Meier method). The results showed that HCC patients with low RBM4 expression had worse overall survival than those with high RBM4 expression (P<0.001). (B) Kaplan–Meier survival curves of disease-free survival in 95 HCC patients. Log-rank tests indicated that patients in the low RBM4 expression group had worse disease-free survival than patients in the high RBM4 expression group (P=0.007).
Abbreviations: RBM4, RNA-binding motif 4; HCC, hepatocellular carcinoma.

Table 2 The Cox proportional hazard regression analyses for overall survival

Variables	No	Univariable analysis		Multivariable analysis
		HR (95% CI)	P-value	HR (95% CI)	P-value
Sex
Female	15	1
Male	80	1.054 (0.524–1.364)	0.568	NA	NA
Age (years)
≤60	72	1
>60	23	1.164 (0.957–2.617)	0.379	NA	NA
AFP (ng/mL)
≤20	34	1
>20	61	1.153 (0.969–1.723)	0.493	NA	NA
Hepatitis B status
Positive	75	1
Negative	20	1.164 (0.668–2.150)	0.164	NA	NA
Liver cirrhosis
Absence	34	1
Presence	61	0.955 (0.654–1.355)	0.317	NA	NA
Child–Pugh classification
A	84	1
B	11	0.668 (0.384–1.325)	0.135	NA	NA
Tumor number
Solitary	42	1		1
Multiple	53	1.962 (1.033–2.517)	0.033	1.723 (1.127–2.698)	0.041
Tumor size
≤5 cm	33	1
>5 cm	62	1.356 (0.922–1.846)	0.327	NA	NA
Capsular formation
Presence	35	1		1
Absence	60	1.898 (1.168–2.258)	0.040	1.696 (1.198–3.158)	0.038
Vascular invasion
Absence	70	1		1
Presence	25	2.468 (1.395–3.650)	0.001	2.698 (1.587–3.648)	0.003
Edmondson–Steiner grade
Low grade (I and II)	49	1
High grade (III and IV)	46	1.538 (0.992–2.765)	0.149	NA	NA
UICC/AJCC stage
I	41	1
II–III	54	1.365 (0.789–2.018)	0.078	NA	NA
BCLC stage
0–A	32	1		1
B–C	63	2.125 (1.158–3.028)	0.041	2.058 (1.105–3.369)	0.045
RBM4 expression
Low	71	1		1
High	24	2.016 (1.283–3.395)	0.022	1.693 (1.498–3.845)	0.033

Note: Bold figures represent P<0.05.

Abbreviations: HR, hazard ratio; CI, confidence interval; NA, not applicable; AFP, alpha feto protein; RBM4, RNA-binding motif 4; BCLC, Barcelona clinic liver cancer; UICC, Union for International Cancer Control; AJCC, American Joint Committee on Cancer.

Table 3 The Cox proportional hazard regression analyses for disease-free survival

Variables	No	Univariable analysis		Multivariable analysis
		HR (95% CI)	P-value	HR (95% CI)	P-value
Sex
Female	15	1
Male	80	1.064 (0.520–1.487)	0.218	NA	NA
Age (years)
≤60	72	1
>60	23	1.969 (0.686–2.073)	0.228	NA	NA
AFP (ng/mL)
≤20	34	1
>20	61	1.039 (0.578–1.633)	0.568	NA	NA
Hepatitis B status
Positive	75	1
Negative	20	1.173 (0.739–2.833)	0.397	NA	NA
Liver cirrhosis
Absence	34	1
Presence	61	0.823 (0.601–1.335)	0.454	NA	NA
Child–Pugh classification
A	84	1
B	11	1.302 (0.663–2.133)	0.369	NA	NA
Tumor number
Solitary	42	1		1
Multiple	53	2.168 (1.662–4.357)	0.037	1.783 (1.569–2.983)	0.041
Tumor size
≤5 cm	33	1
>5 cm	62	1.386 (0.567–2.584)	0.348	NA	NA
Capsular formation
Presence	35	1		1
Absence	60	1.683 (1.128–3.689)	0.031	1.562 (1.081–3.268)	0.037
Vascular invasion
Absence	70	1		1
Presence	25	2.073 (1.288–2.892)	0.018	2.284 (1.304–3.722)	0.021
Edmondson–Steiner grade
Low grade (I and II)	49	1
High grade (III and IV)	46	1.838 (0.684–2.345)	0.287	NA	NA
UICC/AJCC stage
I	41	1
II–III	54	1.584 (0.878–2.285)	0.099	NA	NA
BCLC stage
0–A	32	1		1
B–C	63	2.567 (1.393–3.125)	0.033	2.382 (1.286–3.653)	0.041
RBM4 expression
Low	71	1		1
High	24	2.694 (1.684–3.845)	0.026	1.683 (1.468–3.689)	0.038

Note: Bold figures represent P<0.05.

Abbreviations: HR, hazard ratio; CI, confidence interval; NA, not applicable; AFP, alpha feto protein; RBM4, RNA-binding motif 4; BCLC, Barcelona clinic liver cancer; UICC, Union for International Cancer Control; AJCC, American Joint Committee on Cancer.