miR-3682-3p directly targets FOXO3 and stimulates tumor stemness in hepatocellular carcinoma via a positive feedback loop involving FOXO3/PI3K/AKT/c-Myc

Table 1 Correlations between FOXO3 expression and the clinicopathological features of hepatocellular carcinoma patients, n (%)

Characteristics	n	FOXO3 expression		P value
		Low	High
Age (yr)
> 50	50	30 (60.00)	20 (40.00)	0.633
≤ 50	40	22 (55.00)	18 (45.00)
Gender
Male	80	46 (57.50)	34 (42.50)	1.000
Female	10	6 (60.00)	4 (40.00)
AJCC stage
I	52	25 (48.08)	27 (51.92)	0.029
II-III	38	27 (71.05)	11 (28.95)
HBsAg
Negative	19	8 (42.11)	11 (57.89)	0.119
Positive	71	44 (61.97)	27 (38.03)
Recurrence
No	41	19 (46.34)	22 (53.76)	0.032
Yes	49	33 (67.35)	16 (32.65)
AFP (μg/L)
> 400	33	19 (57.6)	14 (42.4)	0.976
≤ 400	57	33 (57.9)	24 (42.1)
Total bilirubin (μmol/L)
>20	15	5 (33.33)	10 (66.67)	0.036
≤ 20	75	47 (62.67)	28 (37.33)
ALT (U/L)
> 45	31	20 (64.52)	11 (35.48)	0.348
≤ 45	59	32 (54.24)	27 (45.76)
GGT
> 40	59	37 (62.7)	22 (37.3)	0.191
≤ 40	31	15 (48.4)	16 (51.6)
Edmondson-Steiner grade
I-II	61	28 (45.90)	33 (54.10)	0.001
III-IV	29	24 (82.76)	5 (17.24)
Tumor number
Single	79	45 (56.97)	34 (45.03)	0.675
Multiple	11	7 (63.64)	4 (36.36)
Tumor size (cm)
> 5	28	24 (85.71)	4 (14.29)	0.001
≤ 5	62	28 (45.16)	34 (54.84)

Table 2 Univariate and multivariate survival analysis of clinicpathological variables of hepatocellular carcinoma patients

Characteristics	Overall survival
	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
FOXO3 expression	0.311	(0.134-0.721)	0.006	0.504	(0.164-1.553)	0.233
Low vs high
Age (yr)	0.721	(0.352-1.476)	0.371
≤ 50 vs > 50
Gender	0.520	(0.124-2.176)	0.371
Male vs female
AJCC stage	2.277	(1.123-4.616)	0.022	1.203	(0.555-2.604)	0.640
I vs II-III
HBsAg	0.667	(0.257-1.736)	0.407
Negative vs positive
Recurrence	87.223	(4.860-1565.443)	0.002
No vs yes
AFP (ng/mL)	0.888	(0.434-1.818)	0.746
≤ 400 vs > 400
Total bilirubin (μmol/L)	1.113	(0.428-2.893)	0.826
≤ 20 vs > 20
ALT (U/L)	1.046	(0.504-2.171)	0.903
≤ 45 vs > 45
GGT (U/L)	0.386	(0.159-0.937)	0.035	0.594	(0.233-1.516)	0.276
≤ 40 vs > 40
Edmondson-Steiner grade	3.664	(1.791-7.497)	< 0.001	1.839	(0.560-3.445)	0.478
I-II vs III-IV
Tumor number	1.810	(0.742-4.417)	0.192
Singlevs vs multiple
Tumor size (cm)	0.504	(0.250-1.018)	0.056
≤ 5 vs > 5