Assessment of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and its mRNA BST2 as serum innovative non-invasive biomarkers: Recent insights into Egyptian patients with hepatitis C virus type 4

doi:10.3748/wjg.v26.i2.168

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World Journal of Gastroenterology

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World J Gastroenterol. Jan 14, 2020; 26(2): 168-183
Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.168

Table 1 Demographic and clinical data of the study participants

Parameters	Healthy control	Naïve	SOF + SIM	SOF + DAC	SOF + DAC + RBV	Relapsed
Parameters	(n = 20)	(n = 30)	(n = 30)	(n = 20)	(n = 20)	(n = 30)
Age (yr)	40.2 ± 5	44.3 ± 6.9	42.2 ± 6.7	42.8 ± 7.2	39.7 ± 5.1	44.1 ± 6.5
Gender (M/F)	16/4	26/4	27/3	19/1	19/1	25/5
ALT (IU/L)	9.2 ± 6.2	37.2 ± 25^b	18.7 ± 8.2^a^d	17.6 ± 5.6^a^d	26.7 ± 2.4^a^d^e^g	23.7 ± 6.9^d
AST (IU/L)	10.3 ± 4.2	34.4 ± 16.4^b	27.4 ± 13.7^b^c	26.9 ± 6.9^b^c	32.7 ± 5.2^b	23.3 ± 6.3^d
Albumin (g/dL)	3.8 ± 0.27	2.7 ± 0.43^b	3.2 ± 0.5^b^d	3.9 ± 0.3^d^h	4 ± 0.4^a^d^h	3 ± 0.4^d
ALP (IU/L)	53.7 ± 6.8	130.6 ± 21^b	86.1 ± 16^b^d	78.4 ± 16^b^d	81.2 ± 12.4^b^d	99.4 ± 11.2^b^f
Bilirubin (mg/dL)	0.9 ± 0.1	1.1 ± 0.4^a	1.2 ± 0.5^b	1.1 ± 0.4	0.9 ± 0.3^c^e	1.2 ± 0.4
INR	1.06 ± 0.07	1.4 ± 0.25^b	1.5 ± 0.25^b	1.3 ± 0.19^b	1.2 ± 0.22^a^d^f^h	1.4 ± 0.27
AFP (ng/mL)	7.6 ± 1.3	15 ± 8.6^b	7.3 ± 0.8^d	7 ± 1^d	6.9 ± 1^d	32 ± 9.6^b^f
PT	11.7 ± 0.5	14.8 ± 2^b	13.7 ± 1.4^b^d	13.1 ± 1.2^b^d	12.6 ± 1.5^d^e	14.1 ± 1.1
Viral load (log copies/mL)	0	6.47 ± 0.7^c	0^d	0^d	0^d	6.38 ± 0.39^f

^aP < 0.05,

^bP < 0.01, vs control group;

^cP < 0.05,

^dP < 0.01, vs naïve group;

^eP < 0.05,

^fP < 0.01, vs SOF + SIM group;

^gP < 0.05,

^hP < 0.01, vs SOF + DAC group. The data are expressed as the mean ± SD. The data were analysed by one-way ANOVA followed by Tukey HSD multiple comparison test. Naïve: Hepatitis C virus naïve patients without any treatment; SOF + SIM: Hepatitis C virus-infected patients treated with sovaldi and simeprevir; SOF + DAC: Hepatitis C virus-infected patients treated with combined therapy sovaldi and daclatasvir; SOF + DAC + RBV: Hepatitis C virus-infected patients treated with triplet therapy sovaldi, daclatasvir and ribavirin; Relapsed: Relapsed HCV patients from SOF + SIM treatment; ALT: Alanine aminotransferases; AST: Aspartate aminotransferases; ALP: Alkaline phosphatase; INR: International normalized ratio AFP: Alfa fetoprotein; PT: Prothrombin time.

Table 2 Pearson’s correlation between studied LncRNA GAS5, LncRNA BISPR, LncRNA HEIH, mRNA BST2 and clinical parameters in the different studied groups

Variables	LncRNA Gas5		LncRNA BISPR		LncRNA HEIH		MRNA BST2
Variables	r	P value	r	P value	r	P value	r	P value
Age (yr)	0.051	0.53	0.138	0.09	0.095	0.24	-0.043	0.60
Sex (M/F)	0.070	0.39	-0.043	0.60	0.037	0.65	-0.062	0.44
ALT (IU/L)	0.332	0.001^c	0.287	0.001^c	-0.072	0.37	-0.194	0.01^a
AST (IU/L)	0.016	0.04^a	0.141	0.08	-0.222	0.006^b	0.008	0.92
Albumin (g/dL)	-0.454	0.001^c	-0.419	0.001^c	-0.0157	0.05	0.434	0.001^c
Bilirubin (mg/dL)	0.088	0.28	0.049	0.54	0.034	0.67	-0.083	0.31
ALP (IU/L)	0.589	0.001^c	0.517	0.001^c	0.044	0.59	-0.346	0.001^c
INR	0.136	0.09	0.172	0.03^a	-0.062	0.45	0.021	0.79
AFP	0.476	0.001^c	0.176	0.03^a	0.640	0.001^c	-0.347	0.001^c
PT	0.405	0.001^c	0.300	0.001^c	0.081	0.32	-0.206	0.01^a
Viral load	0.276	0.001^c	0.374	0.001^c	0.056	0.49	-0.284	0.001^c
(log copies/mL)	0.276	0.001^c	0.374	0.001^c	0.056	0.49	-0.284	0.001^c
LncRNA Gas5			0.607	0.001^c	0.318	0.001^c	-0.465	0.001^c
LncRNA BST2	0.607	0.001^c			0.040	0.62	-0.371	0.001^c
LncRNA HEIH	0.318	0.001^c	0.040	0.62			-0.235	0.004^b
mRNA BST2	-0.465	0.001^c	-0.371	0.001^c	-0.235	0.004^b

^aP < 0.05,

^bP < 0.01,

^cP < 0.001, indicates statistical signiﬁcance. ALT: Alanine aminotransferases; AST: Aspartate aminotransferases; ALP: Alkaline phosphatase; INR: International normalized ratio AFP: Alfa fetoprotein; PT: Prothrombin time.

Table 3 Factors that discriminate between naïve patients (n = 30) and healthy controls (n = 20) using logistic regression analysis

Parameter	B	SE	P value	Odds ratio	Odds ratio (95%CI)
Univariate analysis
LncRNA-Gas5	1.95	0.675	0.004^b	7.08	1.88-26.59
LncRNA-BISPR	1.2	0.421	0.004^b	3.32	1.45-7.57
LncRNA-HEIH	-3.8	1.079	0.005^b	0.02	0.003-0.184
mRNA BST2	-1.71	0.606	0.003^b	0.17	0.05-0.587
ALT (IU/L)	0.2	0.06	0.001^b	1.22	1.09-1.38
AST (IU/L)	0.42	0.135	0.002^b	1.52	1.16-1.98
AFP (ng/ml)	0.358	0.165	0.03^a	1.43	1.03-1.97
ALP (IU/L)	0.209	0.067	0.002^b	1.23	1.080-1.4
Albumin (mg/dl)	-20.26	9.95	0.04^a	0.01	0.00-0.471
Multiple analysis
LncRNA-Gas5	2.4	0.766	0.002^b	11.12	2.47-49.88
mRNA-BST2	-2.71	1.013	0.007^b	0.066	0.009-0.484

^aP < 0.05,

^bP < 0.01, indicates statistical signiﬁcance.

Table 4 Factors that predict response to SOF + SIM (n = 30), SOF + DAC (n = 20) or SOF + DAC + RBV (n = 20) treatment regimens using logistic regression analysis

Paramete	B	SE	P value	Odds ratio	Odds ratio (95%CI)
Univariate analysis (SOF + SIM)
LncRNA-Gas5	2.135	0.583	< 0.001^c	8.45	2.69-26.50
LncRNA-BISPR	1.733	0.482	< 0.001^c	5.65	2.19-14.56
mRNA BST2	-2.029	0.501	< 0.001^c	0.13	0.04-0.351
ALT (IU/L)	0.084	0.03	0.005^b	1.08	1.025-1.153
AFP (ng/mL)	0.715	0.299	0.01^a	2.044	1.137-3.675
ALP (IU/L)	0.209	0.067	0.002^b	1.232	1.080-1.405
Albumin (mg/dL)	-1.947	0.635	0.002^b	0.143	0.041-0.495
Multivariate analysis
LncRNA-Gas5	1.397	0.704	0.04^a	4.04	1.01-16.073
LncRNA-BISPR	1.613	820	0.04^a	5.01	1.007-25.02
mRNA BST2	-3.149	1.307	0.01^a	0.043	0.003-0.556
Univariate analysis (SOF + DAC)
LncRNA-Gas5	1.54	0.48	0.002^b	4.69	1.80-12.26
LncRNA-BISPR	1.86	0.61	0.003^b	6.43	1.91-21.59
mRNA BST2	-1.677	0.415	< 0.001^c	0.187	0.083-0.422
ALT (IU/L)	0.125	0.048	0.01^a	1.13	1.031-1.245
AFP (ng/mL)	0.715	0.299	0.01^a	2.044	1.137-3.675
ALP (IU/L)	0.729	0.296	0.01^a	2.073	1.161-3.699
Multivariate analysis
LncRNA-Gas5	1.17	0.54	0.03^a	3.05	1.06-8.79
LncRNA-BISPR	1.42	0.69	0.03^a	4.17	1.07-16.1
Univariate analysis (SOF + DAC + RBV)
LncRNA-Gas5	1.12	0.33	0.001^b	3.07	1.6-5.88

^aP < 0.05,

^bP < 0.01, indicates statistical signiﬁcance. ALT: Alanine aminotransferases; AFP: Alfa fetoprotein; ALP: Alkaline phosphatase.

Table 5 Factors that predict relapsed hepatitis C virus patients (n = 30) from SOF + SIM therapy (n = 30) using logistic regression analysis

Parameter	B	SE	P value	Odds ratio	Odds ratio (95%CI)
Univariate analysis
LncRNA-Gas5	2.35	0.564	< 0.001^b	10.48	3.47-31.67
LncRNA-BISPR	2.27	0.555	< 0.001^b	9.69	3.26-28.73
LncRNA-HEIH	1.99	0.599	0.001^b	7.31	2.26-23.63
mRNA BST2	-3.15	0.858	< 0.001^b	0.042	0.08-0.228
ALT (IU/L)	0.87	0.037	0.01^a	1.09	1.01-1.17
ALP (IU/L)	0.069	0.022	0.002^b	1.07	1.02-1.11
Multivariate analysis
LncRNA-Gas5	1.46	0.69	0.03^a	4.322	1.12-16.70
LncRNA-HEIH	1.4	0.714	0.04^a	8.885	1.00-16.51

^aP < 0.05,

^bP < 0.01, indicates statistical signiﬁcance. ALT: Alanine aminotransferases; ALP: Alkaline phosphatase.

Citation: El Samaloty NM, Shabayek MI, Ghait RS, El-Maraghy SA, Rizk SM, El-Sawalhi MM. Assessment of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and its mRNA BST2 as serum innovative non-invasive biomarkers: Recent insights into Egyptian patients with hepatitis C virus type 4. World J Gastroenterol 2020; 26(2): 168-183
URL: https://www.wjgnet.com/1007-9327/full/v26/i2/168.htm
DOI: https://dx.doi.org/10.3748/wjg.v26.i2.168