Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis

Table 1 Clinicopathological characteristic of colon cancer tissue microarray

Characteristic		All patients (n = 90)
Age, mean ± SD		64.11 ± 13.17
Gender, n (%)	Female	46 (51.11)
	Male	44 (48.89)
Histologic grade, n (%)	Grade II	57 (63.33)
	Grade III	33 (36.67)
Maximum tumor diameter, median (Q1, Q3)		5.40 (4.00, 7.00)
Tumor location, n (%)	Right colon	42 (46.67)
	Left colon	41 (45.56)
	Unknown	7 (7.78)
Lympho-vascular invasion, n (%)	No	60 (66.67)
	Yes	30 (33.33)
Perineural invasion, n (%)	No	74 (82.22)
	Yes	16 (17.78)
Pathologic T stage, n (%)	T2	9 (10.00)
	T3	31 (34.44)
	T4a	41 (45.56)
	T4b	9 (10.00)
Pathologic N stage, n (%)	N0	56 (62.22)
	N1	18 (20.00)
	N2	16 (17.78)
Clinical M stage, n (%)	M0	86 (95.56)
	M1	4 (4.44)
Disease stage, n (%)	I	9 (10.00)
	II	45 (50.00)
	III	32 (35.56)
	IV	4 (4.44)
CD8 positive rate, n (%)	< 5%	60 (66.67)
	≥ 5%	30 (33.33)
PD-L1 positive rate, n (%)	< 5%	63 (70.00)
	≥ 5%	27 (30.00)
PD1 positive rate, n (%)	< 5%	66 (73.33)
	≥ 5%	24 (26.67)
KRAS mutant status, n (%)	Mutant	28 (31.11)
	Wild type	62 (68.89)

PD-L1: Programmed death ligand 1; PD1: Programmed cell death 1.

Table 2 Chi-square tests between transglutaminase 2 level and clinicopathological characteristic in entire patient cohort, n (%)

Clinical parameters	TGM2 expression level		χ2	P value
	Low (n = 44)	High (n = 46)
Age			0.148	0.701
≤ 60	18 (40.91)	17 (36.96)
> 60	26 (59.09)	29 (63.04)
Gender			0.046	0.829
Female	23 (52.27)	23 (50.00)
Male	21 (47.73)	23 (50.00)
Histologic grade			0.667	0.414
Grade II	26 (59.09)	31 (67.39)
Grade III	18 (40.91)	15 (32.61)
Tumor size			0.525	0.469
< 5 cm	14 (31.82)	18 (39.13)
≥ 5 cm	30 (68.18)	28 (60.87)
Lympho-vascular invasion			6.183	0.013a
No	34 (77.27)	24 (52.17)
Yes	10 (22.73)	22 (47.83)
Perineural invasion			2.423	0.120
No	39 (88.64)	35 (76.09)
Yes	5 (11.36)	11 (23.91)
Pathologic T stage			1.076	0.300
T2-T3	22 (50.00)	18 (39.13)
T4a-T4b	22 (50.00)	28 (60.87)
Pathologic N stage			0.073	0.787
N0	28 (63.64)	28 (60.87)
N1-2	16 (36.36)	18 (39.13)
Clinical M stage			0.000	1.000
M0	42 (95.45)	44 (95.65)
M1	2 (4.55)	2 (4.35)
Disease stage			0.067	0.796
Stage I & II	27 (61.36)	27 (58.70)
Stage III & IV	17 (38.64)	19 (41.30)
CD8 positive rate			0.022	0.881
< 5%	29 (65.91)	31 (67.39)
≥ 5%	15 (34.09)	15 (32.61)
PD-L1 positive rate			0.686	0.408
< 5%	29 (65.91)	34 (73.91)
≥ 5%	15 (34.09)	12 (26.09)
PD-1 positive rate			1.699	0.192
< 5%	35 (79.55)	31 (67.39)
≥ 5%	9 (20.45)	15 (32.61)
KRAS mutant status			0.098	0.754
Wild type	31 (70.45)	31 (67.39)
Mutation	13 (29.55)	15 (32.61)

^aP < 0.05.

TGM2: Transglutaminase 2; PD-L1: Programmed death ligand 1; PD1: Programmed cell death 1.

Table 3 Chi-square tests between transglutaminase 2 level and clinicopathological characteristic in KRAS mutant patients, n (%)

Clinical parameters	TGM2 expression level		P value
	Low (n = 13)	High (n = 15)
Age			0.476
≤ 60	5 (38.46)	8 (53.33)
> 60	8 (61.54)	7 (46.67)
Gender			1.000
Female	7 (53.85)	7 (46.67)
Male	6 (46.15)	8 (53.33)
Histologic grade			1.000
Grade II	8 (61.54)	10 (66.67)
Grade III	5 (38.46)	5 (33.33)
Tumor size			0.700
< 5 cm	6 (46.15)	5 (33.33)
≥ 5 cm	7 (53.85)	10 (66.67)
Lympho-vascular invasion			0.670
No	9 (69.23)	12 (80.00)
Yes	4 (30.77)	3 (20.00)
Perineural invasion			0.044a
No	13 (100.00)	10 (66.67)
Yes	0 (0.00)	5 (33.33)
Pathologic T stage			0.445
T2-T3	7 (53.85)	5 (33.33)
T4a-T4b	6 (46.15)	10 (66.67)
Pathologic N stage			0.460
N0	9 (69.23)	8 (53.33)
N1-2	4 (30.77)	7 (46.67)
Clinical M stage			1.000
M0	13 (100.00)	14 (93.33)
M1	0 (0.00)	1 (6.67)
Disease stage			0.276
Stage I & II	9 (69.23)	7 (46.67)
Stage III & IV	4 (30.77)	8 (53.33)
CD8 positive rate			1.000
< 5%	9 (69.23)	11 (73.33)
≥ 5%	4 (30.77)	4 (26.67)
PD-L1 positive rate			1.000
< 5%	9 (69.23)	10 (66.67)
≥ 5%	4 (30.77)	5 (33.33)
PD-1 positive rate			1.000
< 5%	9 (69.23)	10 (66.67)
≥ 5%	4 (30.77)	5 (33.33)

^aP < 0.05.

TGM2: Transglutaminase 2; PD-L1: Programmed death ligand 1; PD1: Programmed cell death 1.