MicroRNAs and clinical implications in hepatocellular carcinoma

Table 1 Demographic data and Child Pugh scoring of the studied groups n (%)

Variable(s)	Group I	Group II	Group III	P value
	HCC group (n = 57)	Cirrhotic group (n = 57)	Control group (n = 57)
Gender
Male	37 (64.91)	39 (68.42)	40 (70.18)	0.8289
Female	20 (35.09)	18 (31.58)	17 (29.82)
Age (mean ± SD) (yr)	55.9 ± 5.194	54.88 ± 9.907	54.3 ± 6.34	0.5087
Child Pugh classification
A	10 (17.54)	15 (26.32)	-	0.527
B	18 (31.58)	16 (28.07)	-
C	29 (50.88)	26 (45.61)	-

HCC: Hepatocellular carcinoma.

Table 2 Imaging characteristics of hepatocellular carcinoma cases

Variables		n (%)
Size (mean ± SD) (range) cm	7.61 ± 3.037 (3.2-14)
Portal veins thrombosis	Yes	10 (17.54)
	No	47 (82.46)
No. of focal lesions	Single	32 (56.14)
	Multiple	25 (43.86)
Site of focal lesions	Right lobe	32 (56.14)
	Left lobe	17 (29.82)
	Both lobes	8 (14.04)
Okuda stage	I	7 (12.28)
	II	23 (40.35)
	III	27 (47.37)

Table 3 Laboratory characteristics among the studied groups

Variable(s)	Group I	Group II	Group III	P	P1	P2	P3
	HCC group (n = 57)	Cirrhotic group (n = 57)	Control group (n = 57)
	mean ± SD	mean ± SD	mean ± SD
ALT (U/L)	60.75 ± 32.63	59.04 ± 68.74	30.18 ± 5.48	< 0.0001	< 0.05	< 0.001	< 0.001
AST (U/L)	86.7 ± 35.1	66.77± 32.07	32.79 ± 7.2	< 0.0001	< 0.01	< 0.001	< 0.001
Total bilirubin (mg/dL)	4.48 ± 4.7	5.2 ± 5.59	0.77 ± 0.18	< 0.0001	> 0.05	< 0.001	< 0.001
Serum albumin (g/dL)	2.54 ± 0.38	2.72 ± 0.53	4.05 ± 0.47	< 0.0001	> 0.05	< 0.001	< 0.001
INR	1.48 ± 0.3	1.54 ± 0.72	0.99 ± 0.07	< 0.0001	> 0.05	< 0.001	< 0.001
Serum α-feto protein (ng/mL)	1418.55 ± 2953.2	41.61 ± 15.78	5.8 ± 1.65	< 0.0001	> 0.05	< 0.001	< 0.001
Serum creatinine (mg/dL)	2.2 ± 1.77	1.64 ± 1.23	0.95 ± 0.16	< 0.0001	> 0.05	< 0.001	< 0.001
Hemoglobin (g/dL)	9.72 ± 1.22	10.02 ± 0.89	12.62 ± 1.1	< 0.0001	> 0.05	< 0.001	< 0.001
Platelet (× 109/L)	98.33 ± 30.83	102.32 ± 33.24	220.93 ± 53.14	< 0.0001	> 0.05	< 0.001	< 0.001
Total leucocytic count (× 109/L)	3.17 ± 0.47	3.39 ± 0.50	6.83 ± 2	< 0.0001	> 0.05	< 0.001	< 0.001

Table 4 MicroRNAs levels among the studied groups

Variable(s)	Group I	Group II	Group III	P	P1	P2	P3
	HCC group (n = 57)	Cirrhotic group (n = 57)	Control group (n = 57)
	Median (range)	Median (range)	Median (range)
MicroRNA 23a	214 (21-218)	211 (21-218)	26 (20-219)	< 0.0001	< 0.05	< 0.001	< 0.001
MicroRNA 34	214 (22-220)	211 (24-218)	25 (20-219)	< 0.0001	> 0.05	< 0.001	< 0.001
MicroRNA 203	26 (21-219)	26 (20-219)	214 (21-225)	< 0.0001	> 0.05	< 0.001	< 0.001
MicroRNA 338	26 (21-219)	26 (21-219)	212 (29-217)	< 0.0001	> 0.05	< 0.001	< 0.001
MicroRNA 16	214 (21-225)	213 (24-218)	25 (20-219)	< 0.0001	> 0.05	< 0.001	< 0.001

P1: Group I vs II; P2: Group I vs III; P3: Group II vs III.

Table 5 Comparison between microRNAs levels in relation to tumour characteristics, α-feto protein level, Okuda staging, and the etiology of liver cirrhosis

MicroRNA 16			MicroRNA 338			MicroRNA 203			MicroRNA 34			MicroRNA 23a			n	Variable(s)
P-value	Range	Median	P-value	Range	Median	P-value	Range	Median	P-value	Range	Median	P-value	Range	Median
0.3910	24-217	212	0.3890	24-219	27	0.2571	22-217	24	0.0558	24-215	213	0.0008a	21-213	211	11	Less than 5 cm	Size of focal lesions
	21-225	214		21-215	25		21-219	26		22-220	215		23-2118	214	46	Equal or more 5 cm
0.3026	23-221	214	0.5352	21-219	26	0.5040	22-219	26	0.8975	24-220	214	0.0001a	21-218	211	32	Single	No. of focal lesions
	21-225	214		22-215	26		21-29	26		22-2119	215		214-218	215	25	multiple
0.9581	29-218	214	0.9247	22-29	26	0.7767	23-29	26	0.8255	22-219	214	0.0795	210-217	215	10	Present	Portal vein thrombosis
	21-225	214		21-219	26		21-219	26		24-220	214		21-218	213	47	Absent
0.8881	22-225	214	0.8295	21-219	26	0.0807	21-217	27	0.3367	22-220	215	0.9736	21-218	214	36	Less than 200 ng/mL	AFP level
	21-221	214		21-215	26		21-219	25		27-219	214		23-217	214	21	Equal or more 200 ng/mL
0.9347	25-217	214	0.1145	24-29	27	0.4488	23-217	26	0.4396	24-215	214	0.0001a	24-213	211	7	Stage I	Okuda stage
	23-221	214		21-219	24		22-219	27		29-220	214		21-218	211	23	Stage II
	21-225	214		22-215	27		21-29	25		22-219	214		211-218	215	27	Stage III
0.1603	23-225	214	0.4405	21-219	26	0.4007	21-219	27	0.7827	24-220	214	0.5433	21-218	214	42	HCV	Etiology of liver cirrhosis
	21-215	211		21-29	26		24-215	25		210-217	214		23-215	214	8	HBV
	25-216	214		24-29	27		23-26	24		22-219	215		210-217	214	7	None

^aThe first column is variable but is here in this copy the last column. HCV: Hepatitis C virus; HBV: Hepatitis B virus.

Table 6 Sensitivity, specificity, positive prediction value, negative prediction value and accuracy of microRNAs and α-feto protein

Variable(s)	Cutoff value	Sensitivity%	Specificity%	Positive predictive value (PPV%)	Negative predictive value (NPV%)	Accuracy
MicroRNA 23a	≥ 210	89.47%	64.91%	56.04%	92.5%	79.3%
MicroRNA 34	≥ 210	89.47%	55.26%	50%	91.3%	79.3%
MicroRNA 203	≥ 24	80.7%	10.53%	31.08%	52.17%	29.6%
MicroRNA 338	≥ 25	63.16%	16.67%	27.48%	47.5%	26.4%
MicroRNA 16	≥ 210	87.72%	57.89%	51.02%	90.4%	75.7%
α-feto protein	≥ 200	73.68%	52.63%	43.75%	80%	78.5%

PPV: Positive predictive value; NPV: Negative predictive value.