Overexpression of Tumour Necrosis Factor-α-Induced Protein 8 is Associated with Prognosis in Colon Cancer

Figures & data

Table 1 Associations of TIPE Expression with Various Clinicopathological Factors of Colon Cancer Patients

Characteristics	n	TIPE Expression		Χ^2	P-value
		High (%)	Low (%)
Total	200	64	136
Follow-up		2–113 months
Survival time		46.88 ± 34.87	69.49±30.50
Age (years)				0.641	0.423
≤ 65	102	30 (46.88%)	72 (52.94%)
> 65	98	34 (53.13%)	64 (47.06%)
Gender				0.787	0.375
Male	92	31 (48.44%)	61 (44.85%)
Female	108	33 (51.56%)	75 (55.15%)
Differentiation				0.146	0.965
Well	15	5 (7.81%)	10 (7.35%)
Moderate	149	47 (73.44%)	102 (75.00%)
Poor	36	12 (18.75%)	24 (17.65%)
Lymphatic invasion				18.100	<0.001
No	121	25 (39.06%)	96 (70.59%)
Yes	79	39 (60.94%)	40 (29.41%)
Tumor stage				0.508	0.257
I+II	11	2 (3.13%)	9 (6.62%)
III+IV	189	62 (96.88%)	127 (93.38%)
Dukes’ stage				17.588	<0.001
Dukes’ A	11	2 (3.13%)	9 (6.62%)
Dukes’ B	110	23 (35.94%)	87 (63.97%)
Dukes’ C	79	39 (60.94%)	40 (29.41%)
Location				8.361	0.004
Left	89	19 (29.69%)	70 (51.47%)
Right	111	45 (70.31%)	66 (48.53%)
Histological type				0.032	0.857
MC	33	11 (17.19%)	22 (16.18%)
NMC	167	53 (82.81%)	114 (83.82%)

Abbreviations: MC, mucinous adenocarcinoma; NMC, non-mucinous adenocarcinoma.

Table 2 Associations of TIPE Expression with Various Clinicopathological Factors of Right-Sided and Left-Sided Colon Cancer Patients

Characteristics	RCC (%)		P-value	LCC (%)		P-value
	Low	High		Low	High
Total	66	45		70	19
Age, years:			0.028			0.617
<60	36	19		36	11
≥60	30	36		34	8
Gender:			0.730			0.324
Male	33	21		28	10
Female	33	24		42	9
Differentiation			0.575			0.203
Well	6	2		4	3
Moderate	48	32		54	15
Poor	12	11		12	1
Lymphatic invasion			<0.001			0.131
No	53	17		43	8
Yes	13	28		27	11
Tumor stage			1.000			0.580
I+II	4	2		5	0
III+IV	62	43		65	19
Dukes’ stage			0.001			0.260
Dukes’ A	4	2		5	0
Dukes’ B	49	15		38	8
Dukes’ C	13	28		27	11
Histological type			0.969			0.784
MC	13	9		9	2
NMC	53	36		61	17

Abbreviations: RCC, right-sided colon cancer; LCC, left-sided colon cancer; MC, mucinous adenocarcinoma; NMC, non-mucinous adenocarcinoma.

Figure 1 The expression of TIPE in different samples. (A) Representative immunohistochemical staining showed low TIPE expression in left-side adjacent normal tissue. (B) Representative immunohistochemical staining showed low TIPE expression in right-side adjacent normal tissue. (C) Expression of TIPE in tumor tissues without lymphatic invasion. (D) Representative immunohistochemical staining showed high TIPE expression in left-side colon cancer. (E) Representative immunohistochemical staining showed high TIPE expression in right-side colon cancer. (F) Expression of TIPE in tumor tissues with lymphatic invasion. (G) Before–after plot showing the immunoreactive score (IRS) of paired tumor tissue and adjacent normal tissue for TIPE. (H) The IRS of TIPE expression in LCC and RCC. (I) IRS of TIPE expression in colon cancer specimens with or without lymph node metastasis. *P<0.01; **P<0.0001.

Table 3 ROC-Related Parameters for Predicting 5-Year Overall Survival

Groups	AUC	95% CI	Specificity (%)	Sensitivity (%)	Youden Index (%)	Cut-off value
All patients	0.645	0.563–0.726	49.4	78.9	0.283	5.5
RCC	0.727	0.630–0.825	65.2	76.9	0.421	5.5
LCC	0.516	0.383–0.648	16.1	99.6	0.127	7.5

Abbreviations: ROC, receiver operating characteristic; AUC, area under the curve; CI, confidence interval; RCC, right-sided colon cancer; LCC, left-sided colon cancer.

Table 4 ROC-Related Parameters for Predicting Lymph Node Metastasis

Groups	AUC	95% CI	Specificity (%)	Sensitivity (%)	Youden Index (%)	Cut-off value
All patients	0.683	0.607–0.759	49.4	79.3	0.287	5.5
RCC	0.760	0.665–0.856	68.3	75.7	0.440	5.5
LCC	0.637	0.521–0.753	39.5	78.4	0.179	4.5

Abbreviations: ROC, receiver operating characteristic; AUC, area under the curve; CI, confidence interval; RCC, right-sided colon cancer; LCC, left-sided colon cancer.

Figure 2 ROC curves of the prediction index value in predicting five-year overall survival of patients with (A) colon cancer; (B) right-sided colon cancer; (C) left-sided colon cancer. ROC curves of the prediction index value in predicting lymph node metastasis of patients with (D) colon cancer; (E) right-sided colon cancer; (F) left-sided colon cancer.

Table 5 Prognostic Value of TIPE Expression and Clinicopathological Factors for the Overall Survival of Colon Cancer Patients by Univariate and Multivariate Analyses with Cox Regression

Variable	Univariate			Multivariate
	HR	CI (95%)	P-value	HR	CI (95%)	P-value
Age (years): >65 vs ≤65	1.529	1.001–2.336	0.050	1.554	1.013–2.385	0.043
Gender: male vs female	0.836	0.549–1.272	0.403
Differentiation: poor vs moderate and well	2.547	1.598–4.059	<0.001	2.444	1.528–3.911	<0.001
Lymphatic invasion: Yes vs no	2.508	1.643–3.829	<0.001	1.999	1.288–3.103	0.002
Depth of invasion: T3+4 vs T1+2	6.378	0.888–45.812	0.066
Tumor location: right vs left	1.178	0.769–1.805	0.452
Histological type: MC vs NMC	1.105	0.633–1.929	0.725
TIPE expression: High vs Low	2.751	1.803–4.197	<0.001	2.353	1.521–3.642	<0.001

Abbreviations: HR, hazard ratio; MC, mucinous adenocarcinoma; NMC, non-mucinous adenocarcinoma.

Figure 3 Kaplan–Meier curves for overall survival according to the (A) age; (B) differentiation; (C) lymph node metastasis; (D) TIPE expression level.