MicroRNAs and clinical implications in hepatocellular carcinoma

doi:10.4254/wjh.v9.i23.1001

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Aug 18, 2017 (publication date) through Mar 6, 2025

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Hepatol. Aug 18, 2017; 9(23): 1001-1007
Published online Aug 18, 2017. doi: 10.4254/wjh.v9.i23.1001

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

Variable(s)	Group I	Group II	Group III	P value
Variable(s)	HCC group (n = 57)	Cirrhotic group (n = 57)	Control group (n = 57)	P value
Gender
Male	37 (64.91)	39 (68.42)	40 (70.18)	0.8289
Female	20 (35.09)	18 (31.58)	17 (29.82)	0.8289
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)
Portal veins thrombosis	No	47 (82.46)
No. of focal lesions	Single	32 (56.14)
No. of focal lesions	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	n	Variable(s)
0.3910	2⁴-2¹⁷	2¹²	0.3890	2⁴-2¹⁹	2⁷	0.2571	2²-2¹⁷	2⁴	0.0558	2⁴-2¹⁵	2¹³	0.0008^a	2¹-2¹³	2¹¹	11	Less than 5 cm	Size of focal lesions
0.3910	2¹-2²⁵	2¹⁴	0.3890	2¹-2¹⁵	2⁵	0.2571	2¹-2¹⁹	2⁶	0.0558	2²-2²⁰	2¹⁵	0.0008^a	2³-2¹¹⁸	2¹⁴	46	Equal or more 5 cm	Size of focal lesions
0.3026	2³-2²¹	2¹⁴	0.5352	2¹-2¹⁹	2⁶	0.5040	2²-2¹⁹	2⁶	0.8975	2⁴-2²⁰	2¹⁴	0.0001^a	2¹-2¹⁸	2¹¹	32	Single	No. of focal lesions
0.3026	2¹-2²⁵	2¹⁴	0.5352	2²-2¹⁵	2⁶	0.5040	2¹-2⁹	2⁶	0.8975	2²-2¹¹⁹	2¹⁵	0.0001^a	2¹⁴-2¹⁸	2¹⁵	25	multiple	No. of focal lesions
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
0.9581	2¹-2²⁵	2¹⁴	0.9247	2¹-2¹⁹	2⁶	0.7767	2¹-2¹⁹	2⁶	0.8255	2⁴-2²⁰	2¹⁴	0.0795	2¹-2¹⁸	2¹³	47	Absent	Portal vein thrombosis
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
0.8881	2¹-2²¹	2¹⁴	0.8295	2¹-2¹⁵	2⁶	0.0807	2¹-2¹⁹	2⁵	0.3367	2⁷-2¹⁹	2¹⁴	0.9736	2³-2¹⁷	2¹⁴	21	Equal or more 200 ng/mL	AFP level
0.9347	2⁵-2¹⁷	2¹⁴	0.1145	2⁴-2⁹	2⁷	0.4488	2³-2¹⁷	2⁶	0.4396	2⁴-2¹⁵	2¹⁴	0.0001^a	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.

Citation: Mohamed AA, Ali-Eldin ZA, Elbedewy TA, El-Serafy M, Ali-Eldin FA, AbdelAziz H. MicroRNAs and clinical implications in hepatocellular carcinoma. World J Hepatol 2017; 9(23): 1001-1007
URL: https://www.wjgnet.com/1948-5182/full/v9/i23/1001.htm
DOI: https://dx.doi.org/10.4254/wjh.v9.i23.1001