Effects of targeted-edited oncogenic insulin-like growth factor-1 receptor with specific-sgRNA on biological behaviors of HepG2 cells

Table 1 Positive rates of insulin-like growth factor-1 receptor and P-glyco protein expression and immunohistochemistry score in hepatocellular carcinoma tissues

Group	n	IHC		χ2 value	P value	IHC score				Z value	P value
		Neg.	Pos.			0	1	2	3
IGF-IR				63.947	< 0.001					9.682	< 0.001
HCC	93	6	87			6	10	67	10
Non-Ca	93	59	34			59	25	9	0
P-gp				58.448	< 0.001					8.941	< 0.001
HCC	93	11	82			11	14	57	12
Non-Ca	93	68	25			68	22	2	0

HCC: Hepatocellular carcinoma; Non-Ca: Non-cancerous tissues; IHC: Immunohistochemistry; IGF-IR: Insulin-like growth factor-1 receptor; Neg: Negative IGF-1R expression; P-gp: P-glyco protein; Pos: Positive IGF-1R expression.

Table 2 Clinicopathological features of insulin-like growth factor-1 receptor and P-glyco protein expression in hepatocellular carcinoma tissues

Group	n	IGF-IR			P-gp
		Pos. n (%)	χ2 value	P value	Pos. n (%)	χ2 value	P value
Sex
Male	78	73 (93.6)	0.288	0.591	69 (88.5)	0.811	0.057
Female	15	14 (93.3)			13 (86.7)
Age
≤ 50 yr	68	63(92.6)	0.012	0.914	59 (86.8)	1.611	0.204
> 50 yr	25	24(96.0)			23 (92.0)
HBsAg
Positive	60	60 (100)	8.844	0.003	58 (96.6)	9.517	0.002
Negative	33	27 (81.8)			24 (72.7)
AFP
≤ 400 μg/L	59	55 (93.2)	0.104	0.747	51 (86.4)	0.154	0.695
> 400 μg/L	34	32 (94.1)			31 (91.2)
Tumor diameter
≤ 5.0 cm	71	67 (94.4)	3.550	0.060	63 (88.7)	3.208	0.073
> 5.0 cm	22	20 (90.9)			19 (86.4)
Differentiation
Well	21	17 (81.0)	4.201	0.040	16 (76.2)	1.484	0.223
Middle	49	47 (95.9)			43 (87.8)
Poor	23	23 (100)	4.819	0.028	23 (100)	6.178	0.022
Cirrhosis
With	66	62 (93.9)	1.014	0.314	58 (87.9)	0.782	0.377
Without	27	25 (92.6)			24 (88.9)
TNM staging
I-II	58	52 (89.7)	2.3461	0.1256	47 (81.0)	6.161	0.013
III-IV	35	35 (100)			35 (100)
Vascular invasion
With	36	35 (97.2)	25.363	< 0.001	36 (100)	24.158	< 0.001
Without	57	42 (73.7)			46 (80.7)
Tumor number
One	74	69 (93.2)	0.082	0.774	65 (87.8)	0.041	0.841
More	19	18 (94.7)			17 (89.5)

AFP: α-fetoprotein; HBsAg: Hepatitis B virus surface antigen; HCC: Hepatocellular carcinoma; IGF-IR: Insulin-like growth factor-1 receptor; TNM: Tumor-node-metastasis.

Table 3 Levels of insulin-like growth factor-1 receptor or P-glycoprotein expression in sera of patients with liver diseases

Group	n	IGF-1R (pg/mL)	P-gp (ng/mL)
HCC	93	758.6 ± 126.4	11.6 ± 5.1
Liver cirrhosis	40	521.4 ± 78.3	7.3 ± 6.3
Chronic hepatitis	40	456.8 ± 82.1	3.7 ± 1.4
Health control	40	421.8 ± 58.6	1.0 ± 0.5
F value		154.501	66.182
q value1		0.689	0.487
P value		< 0.001	< 0.001

¹Compared between hepatocellular carcinoma group and liver cirrhosis group. HCC: Hepatocellular carcinoma; IGF-1R: Insulin-like growth factor-1 receptor; P-gp: P-glyco protein.

Table 4 Edited IGF-1R increasing HepG2 cell sensitivity to anti-cancer drugs

Group	Control	Neg-sgRNA	Sg-IGF1R2	F value	q value1	P value
Sorafenib
0.0 nmol/L	0.297 ± 0.06	0.310 ± 0.07	0.199 ± 0.07	1.361	2.604	0.026
2.5 nmol/L	0.326 ± 0.10	0.335 ± 0.11	0.188 ± 0.05	100.00	3.364	0.007
5.0 nmol/L	0.337 ± 0.11	0.318 ± 0.05	0.191 ± 0.06	3.316	2.854	0.017
10.0 nmol/L	0.331 ± 0.05	0.284 ± 0.17	0.152 ± 0.09	1.494	3.085	0.012
20.0 nmol/L	0.093 ± 0.03	0.084 ± 0.02	0.033 ± 0.04	6.499	0.464	0.009
Oxaliplation
0.0 μmol/L	2.391 ± 0.30	2.351 ± 0.17	1.429 ± 0.27	51.91	0.874	0.001
5.0 μmol/L	1.064 ± 0.21	1.014 ± 0.05	0.677 ± 0.08	6.891	4.218	0.002
10.0 μmol/L	0.659 ± 0.16	0.575 ± 0.13	0.417 ± 0.14	1.515	2.768	0.020
20.0 μmol/L	0.288 ± 0.12	0.280 ± 0.08	0.148 ± 0.08	36.000	2.819	0.018
40.0 μmol/L	0.164 ± 0.05	0.162 ± 0.07	0.099 ± 0.04	1.000	2.815	0.018

¹Compared with the control group (n = 6).