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 [DOI: 10.4251/wjgo.v16.i9.3913]
Corresponding Author of This Article
Fang Su, Doctor, MD, PhD, Academic Research, Researcher, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, No. 287 Changhuai Road, Longzihu District, Bengbu 233000, Anhui Province, China. sufang2899@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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
High expression
Low expression
High expression
16
69
85
12.163
< 0.001
Low expression
20
21
41
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
Low (n = 41)
High (n = 85)
Sex, n (%)
Female
23
5 (3.9)
18 (14.3)
1.495
0.221
Male
103
36 (28.6)
67 (53.2)
Age
≤ 65 years
91
32 (25.4)
59 (46.8)
1.028
0.311
> 65 years
35
9 (7.2)
26 (20.6)
Viral hepatitis, n (%)
Yes
110
35 (27.8)
75 (59.5)
0.205
0.651
No
16
6 (4.8)
10 (7.9)
Liver cirrhosis, n (%)
Yes
61
20 (15.9)
41 (32.5)
0.003
0.956
No
65
21 (16.7)
44 (34.9)
AFP (ng/mL), n (%)
≤ 25
52
24 (19.0)
32 (25.4)
4.888
0.027
> 25
74
17 (14.5)
53 (42.1)
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)
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)
Table 4 Univariate analysis of clinicopathological factors and overall survival in 126 hepatocellular carcinoma patients
Characteristic
P value
HR
95%CI
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
Table 5 Cox multivariate analysis of prognostic factors in hepatocellular carcinoma patients
Characteristic
B
SE
Wald
P value
HR
95%CI
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
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
Table 7 Immune checkpoints associated with protein tyrosine phosphatase non-receptor 2 in hepatocellular carcinoma
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