Protein tyrosine phosphatase non-receptor II: A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma

doi:10.4251/wjgo.v16.i9.3913

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Sep 15, 2024 (publication date) through Feb 12, 2025

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World Journal of Gastrointestinal Oncology

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1948-5204

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

Clinical and Translational Research

World J Gastrointest Oncol. Sep 15, 2024; 16(9): 3913-3931
Published online Sep 15, 2024. doi: 10.4251/wjgo.v16.i9.3913

Table 1 Clinical information of patients in high and low protein tyrosine phosphatase non-receptor 2 expression groups from The Cancer Genome Atlas database

Characteristic	Low expression (n = 185)	High expression (n = 185)
T stage, n (%)
T1	96 (51.9)	85 (45.9)
T2	46 (24.9)	47 (25.4)
T3	35 (18.9)	45 (24.4)
T4	6 (3.2)	8 (4.3)
Unknown	2 (1.1)	0 (0)
N stage, n (%)
N0	126 (68.1)	126 (68.1)
N1	21 (11.4)	3 (1.6)
N2-3	38 (20.5)	56 (30.3)
M stage, n (%)
M0	135 (73)	131 (70.8)
M1	22 (11.9)	22 (11.9)
MX	28 (15.1)	32 (17.3)
Clinical stage, n (%)
I	91 (49.2)	80 (43.2)
II	43 (23.2)	42 (22.7)
III	38 (20.6)	47 (25.4)
IV	3 (1.6)	2 (1.1)
Unknown	10 (5.4)	14 (7.6)
Age, n (%)
≤ 65 years	105 (56.8)	127 (68.6)
> 65 years	80 (43.2)	58 (31.4)
Unknown	0 (0)	0 (0)
Sex, n (%)
Female	46 (24.9)	75 (40.5)
Male	139 (75.1)	110 (59.5)
Unknown	0 (0)	0 (0)
Grade, n (%)
G1	33 (17.8)	22 (11.9)
G2	92 (49.7)	85 (46.0)
G3	54 (29.2)	67 (36.2)
G4	4 (2.2)	8 (4.3)
Unknown	2 (1.1)	3 (1.6)

Table 2 Protein tyrosine phosphatase non-receptor 2 expression in hepatocellular carcinoma tumor tissues and paracancerous tissues

Tumor tissue	Paracancer tissue		Total	χ²	P value
Tumor tissue	High expression	Low expression	Total	χ²	P value
High expression	16	69	85	12.163	< 0.001
Low expression	20	21	41	12.163
Total	36	90

Table 3 Clinical information of high and low protein tyrosine phosphatase non-receptor 2 expression groups of patients from the Bengbu Medical College database

Characteristic	Total (n)	PTPN2 expression		χ²	P value
Characteristic	Total (n)	Low (n = 41)	High (n = 85)	χ²	P value
Sex, n (%)
Female	23	5 (3.9)	18 (14.3)	1.495	0.221
Male	103	36 (28.6)	67 (53.2)	1.495	0.221
Age
≤ 65 years	91	32 (25.4)	59 (46.8)	1.028	0.311
> 65 years	35	9 (7.2)	26 (20.6)	1.028	0.311
Viral hepatitis, n (%)
Yes	110	35 (27.8)	75 (59.5)	0.205	0.651
No	16	6 (4.8)	10 (7.9)	0.205	0.651
Liver cirrhosis, n (%)
Yes	61	20 (15.9)	41 (32.5)	0.003	0.956
No	65	21 (16.7)	44 (34.9)	0.003	0.956
AFP (ng/mL), n (%)
≤ 25	52	24 (19.0)	32 (25.4)	4.888	0.027
> 25	74	17 (14.5)	53 (42.1)	4.888	0.027
Tumor size, n (%)
≤ 5 cm	65	23 (18.3)	42 (33.3)	0.495	0.482
> 5 cm	61	18 (14.3)	43 (34.1)	0.495	0.482
Degree of differentiation, n (%)
Undifferentiated	29	7 (5.6)	22 (17.5)	1.324	0.516
Moderately differentiated	76	26 (20.6)	50 (39.7)
Highly differentiated	21	8 (6.3)	13 (10.3)

PTPN2: Protein tyrosine phosphatase non-receptor 2; AFP: α-fetoprotein.

Table 4 Univariate analysis of clinicopathological factors and overall survival in 126 hepatocellular carcinoma patients

Characteristic	P value	HR	95%CI
Characteristic	P value	HR	Lower	Upper
Sex	0.940	0.977	0.532	1.792
Age	0.334	0.762	0.439	1.322
Hepatitis virus coinfection	0.838	1.585	0.441	1.942
Liver cirrhosis	0.018	1.802	1.109	2.930
AFP level	0.258	1.326	0.813	2.163
Tumor size	0.649	1.119	0.689	1.818
Degree of differentiation	0.967	0.992	0.683	1.441
PTPN2	0.018	1.942	1.123	3.359

PTPN2: Protein tyrosine phosphatase non-receptor 2; AFP: α-fetoprotein; HR: Hazard ratio; CI: Confidence interval.

Table 5 Cox multivariate analysis of prognostic factors in hepatocellular carcinoma patients

Characteristic	B	SE	Wald	P value	HR	95%CI
Characteristic	B	SE	Wald	P value	HR	Lower	Upper
Age	-0.272	0.283	0.926	0.336	0.762	0.438	1.326
AFP level	0.082	0.258	0.102	0.749	1.086	0.655	1.799
Liver cirrhosis	0.586	0.254	5.303	0.021	1.796	1.091	2.958
Degree of differentiation	0.138	0.250	0.303	0.582	1.148	0.703	1.875
PTPN2 expression	0.667	0.282	5.607	0.018	1.949	1.122	3.386

PTPN2: Protein tyrosine phosphatase non-receptor 2; AFP: α-fetoprotein; HR: Hazard ratio; CI: Confidence interval.

Table 6 Protein tyrosine phosphatase non-receptor 2 oncogenic pathway parameters in Gene Set Enrichment Analysis

GeneSet	NES	NOM P value	FDR Q value
KEGG_OOCYTE_MEIOSIS	2.15	0.000	0.000
PROGESTERONE_MEDIATED_OOCYTE_MATURATION	2.09	0.000	0.004
PHOSPHATIDYLINOSITOL_SIGNALING_SYSTEM	2.03	0.000	0.006
INOSITOL_PHOSPHATE_METABOLISM	2.03	0.000	0.005
NEUROTROPHIN_SIGNALING_PATHWAY	2.02	0.000	0.005
PANCREATIC_CANCER	2.02	0.000	0.004
PATHWAYS_IN_CANCER	2.01	0.000	0.003
REGULATION_OF_AUTOPHAGY	2.01	0.000	0.003
ENDOCYTOSIS	2.00	0.000	0.004
UBIQUITIN_MEDIATED_PROTEOLYSIS	1.99	0.000	0.004
NOTCH_SIGNALING_PATHWAY	1.99	0.000	0.003
REGULATION_OF_ACTIN_CYTOSKELETON	1.98	0.000	0.003
CELL_CYCLE	1.97	0.000	0.004
APOPTOSIS	1.97	0.000	0.003
FC_GAMMA_R_MEDIATED_PHAGOCYTOSIS	1.97	0.000	0.003
JAK_STAT_SIGNALING_PATHWAY	1.97	0.002	0.003
MAPK_SIGNALING_PATHWAY	1.96	0.000	0.003
SPLICEOSOME	1.96	0.000	0.003
SMALL_CELL_LUNG_CANCER	1.96	0.000	0.003
INSULIN_SIGNALING_PATHWAY	1.95	0.000	0.003

NES: Normalized Enrichment Score; NOM: Nominal; FDR: False discovery rate.

Table 7 Immune checkpoints associated with protein tyrosine phosphatase non-receptor 2 in hepatocellular carcinoma

Gene	Correlation	P value
ADORA2A	0.151	0.0036^a
BTLA	0.211	0^a
CD160	0.164	0.0015^a
CD244	0.099	0.0574
CD274	-0.012	0.817
CD96	0.305	0^a
CSF1R	0.214	0^a
CTLA4	0.307	0^a
HAVCR2	0.315	0^a
IDO1	0.075	0.15
IL10RB	0.229	0^a
KDR	-0.187	0.0003^a
LAG3	0.185	0.0003^a
LGALS9	0.309	0^a
PDCD1	0.344	0^a
PDCD1LG2	0.139	0.0074^a
PVRL2	0.217	0^a
TGFB1	0.34	0^a
TGFBR1	0.121	0.019^a
TIGIT	0.268	0^a
VTCN1	0.11	0.0333^a
C10orf54	0.084	0.104
CD27	0.284	0^a
CD276	0.326	0^a
CD28	0.119	0.022^a
CD40	-0.11	0.0336^a
CD40LG	0.291	0^a
CD48	0.335	0^a
CD80	0.215	0^a

^aP < 0.05.

Citation: Li HY, Jing YM, Shen X, Tang MY, Shen HH, Li XW, Wang ZS, Su F. Protein tyrosine phosphatase non-receptor II: A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16(9): 3913-3931
URL: https://www.wjgnet.com/1948-5204/full/v16/i9/3913.htm
DOI: https://dx.doi.org/10.4251/wjgo.v16.i9.3913