New stem cell autophagy surrogate diagnostic biomarkers in early-stage hepatocellular carcinoma in Egypt: A pilot study

doi:10.4254/wjh.v13.i12.2137

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World Journal of Hepatology

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1948-5182

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World J Hepatol. Dec 27, 2021; 13(12): 2137-2149
Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.2137

Table 1 The ages in the different groups of the study (mean ± SD)

Age	HCC (n = 34)	Chronic liver infection (n = 11)	Control (n = 5)	F¹	P value
	58.88 ± 8.08	56.18 ± 16.26	55.40 ± 22.09	0.34	0.72 NS

¹One-way analysis of variance. HCC: Hepatocellular carcinoma; NS: Non-significant; SD: Standard deviation.

Table 2 Significance of the differences in laboratory data between the three study groups (mean ± SD)

Variable	HCC (n = 34)	Chronic liver infection (n = 11)	Control (n = 5)	F¹	P value
INR	1.37^a± 0.20	1.35^a± 0.30	1.07^b± 0.08	3.93	0.03 S
Serum albumin (g/dL)	2.94 ± 0.42	3.03 ± 0.73	3.40 ± 0.25	1.95	0.15 NS
AST²(IU/L)	50.00^a± 38.00–102.00	23.00^b± 15.00–39.00	15.00^b± 14.00–18.00	16.21	< 0.001 HS
ALT²(IU/L)	40.50^a± 28.00–73.30	22.00 ± 15.00–38.00	10.00^b± 8.00–15.00	12.69	0.002 HS
Total bilirubin²(mg/dL)	1.60^a± 1.10–2.20	1.10 ± 0.50–1.60	0.40^b± 0.30–0.50	14.91	0.001 HS
Direct bilirubin²(mg/dL)	0.70^a± 0.50–1.10	0.30^b± 0.10–0.60	0.10^b± 0.10–0.20	15.84	< 0.001 HS

¹One-way analysis of variance (a, b Post-hoc test).

²Kruskal–Wallis test (median and interquartile range).

^aP < 0.05.

^bP < 0.01.

ALT: Alanine transaminase; AST: Aspartate transaminase; HCC: Hepatocellular carcinoma; HS: Highly significant; INR: International normalized ratio; NS: Non-significant; SD: Standard deviation.

Table 3 Hepatitis virus B and C infections in the three study groups

Variable		HCC (n = 34), (%)	Chronic liver infection (n = 11), (%)	Control (n = 5), (%)	(X²)¹	P value
HCVAb	Positive	30 (88.2)	11 (100.0)	0 (0.0)	18.32 FE	< 0.001 HS
HCVAb	Negative	4 (11.8)	0 (0.0)	5 (100.0)	18.32 FE	< 0.001 HS
HBsAg	Positive	2 (5.9)	0 (0.0)	0 (0.0)	0.78 FE	1.00 NS
HBsAg	Negative	32 (94.1)	11 (100.0)	5 (100.0)	0.78 FE	1.00 NS

¹The chi-square test (FE: Fisher’s exact test). HBsAg: Hepatitis B virus surface antigen; HCC: Hepatocellular carcinoma; HCVAb: Hepatitis C virus antibody; HS: Highly significant; NS: Non-significant.

Table 4 Expression level of hsa-miR-519d-3p, ACTB, RNU6, and SQSTM1 between the three study groups (mean ± SD)

Variable	HCC (n = 34)	Chronic liver infection (n = 11)	Control (n = 5)	F¹	P value
Ct (ACTB)	30.65^a± 4.21	25.82^b± 2.31	27.34^b± 2.00	7.69	0.001 HS
Ct (RNU6)	36.03 ± 2.92	36.36 ± 2.82	38.55 ± 0.96	1.78	0.18 NS
Ct (miR-519d)	30.08^a± 3.00	33.61^b± 2.78	38.05^c± 1.08	20.48	< 0.001 HS
mRNA-SQSTM1	36.14 ± 3.17	34.89 ± 2.30	38.38 ± 1.86	2.48	0.10 NS
DCT (miR-519d)	−5.95^a± 1.98	−2.75^b± 0.89	−0.50^c± 0.40	31.17	< 0.001 HS
DDCT (miR-519d)	−5.59^a± 1.98	−2.39^b± 0.89	−0.14^c± 0.40	31.17	< 0.001 HS
RQ (miR-519d)²	41.94^a± 18.25–139.10	5.98^b± 3.14–8.28	1.17^c± 1.16–1.21	28.46	< 0.001 HS
DCT (SQSTM1)	5.49^a± 1.83	9.07^b± 0.70	11.04^c± 0.58	41.08	< 0.001 HS
DDCT (SQSTM1)	−5.51^a± 1.83	−1.93^b± 0.70	0.04^c± 0.58	41.08	< 0.001 HS
RQ (SQSTM1)²	33.91^a± 14.83–132.51	3.68^b± 2.28–5.50	0.84^c± 0.76–0.99	32.54	< 0.001 HS

¹One-way analysis of variance (a, b post-hoc test).

²Kruskal–Wallis test (median and interquartile range).

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

Ct: Threshold cycle; HS: Highly significant; NS: Non-significant.

Table 5 Alpha-fetoprotein laboratory results in the three subgroups

Variable	HCC (n = 34), median (IQR)	Chronic liver disease (n = 11), median (IQR)	Control (n = 5), median (IQR)		P value
AFP¹(ng/mL) by ELISA	62.60^a(8.20–600.80)	3.50^b(2.50–20.00)	0.70^c(0.50–1.00)	19.17	< 0.001 HS

¹Kruskal–Wallis test (median and interquartile range).

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

AFP: Alpha-fetoprotein; ELISA: Enzyme-linked immunosorbent assay; HCC: Hepatocellular carcinoma; HS: Highly significant; IQR: Interquartile range.

Table 6 Clinical and radiological characteristics of hepatocellular carcinoma lesions.

Variable		mean ± SD
Child–Pugh score		6.76 ± 1.44
		n (%)
Cirrhosis	Cirrhosis	27 (79.4)
Cirrhosis	No cirrhosis	7 (20.6)
BCLC stage	Stage A (early)	31 (91.2)
BCLC stage	Stage D (late)	3 (8.8)
Child–Pugh classification	A	17 (50.0)
	B	14 (41.2)
	C	3 (8.8)
Average tumor size	> 3 cm	3 (8.8)
Average tumor size	< 3 cm	31 (91.2)

BCLC: Barcelona Clinic Liver Cancer; SD: Standard deviation.

Citation: Yosef T, Ibrahim WA, Matboli M, Swilam AA, El-Nakeep S. New stem cell autophagy surrogate diagnostic biomarkers in early-stage hepatocellular carcinoma in Egypt: A pilot study . World J Hepatol 2021; 13(12): 2137-2149
URL: https://www.wjgnet.com/1948-5182/full/v13/i12/2137.htm
DOI: https://dx.doi.org/10.4254/wjh.v13.i12.2137