Prognostic significance of preoperative IKBKE expression in esophageal squamous cell carcinoma

Figures & data

Table 1 Clinical and histopathological characteristics of 118 esophageal squamous cell carcinoma patients

Characteristic	Patients, n	Percentage
Gender
Female	23	19.5
Male	95	80.5
Age (years)
Mean ± SD	61.1±8.2
Median	60.5
Tumor location
Cervical	3	2.5
Upper	12	10.2
Middle	66	55.9
Lower	37	31.4
Tumor length (cm)
Mean ± SD	3.84±1.59
Median (range)	3.5 (0.5–8.5)
T stage
T1	17	14.4
T2	26	22.0
T3	67	56.8
T4	8	6.8
Differentiation grade
Well	32	27.1
Middle	51	43.2
Poor	35	29.7
Lymphatic metastasis
Yes	47	39.8
No	71	60.2
Lymphatic metastasis number
<2	21	17.8
≥2	26	22.0
Mean ± SD	2.55±2.28
Median (range)	2 (1–10)
Tumor thrombus
Yes	5	4.2
No	113	95.8
TNM stage
I	18	15.3
II	57	48.3
III	43	36.4
IKBKE expressiona
High	73	61.9
Low	45	38.1

Note:

a The proportion of IKBKE-expressing cells that exceeded 25% was grouped into high expression, and if not, then low expression.

Abbreviations: T, tumor; TNM, pathological tumor node metastasis; IKBKE, inhibitor of NF-κB kinase epsilon.

Figure 1 Inhibitor of NF-κB kinase epsilon (IKBKE, IKKε) was significantly upregulated in esophageal squamous cell carcinoma (ESCC). Immunohistochemistry assays of IKBKE expression in 118 ESCC patients. (A) Tumor tissues with low IKKε expression. (B) High IKBKE expression in ESCC tissues. The panels were observed at medium magnification (×200). Scale bars, 1:100 μm.

Figure 2 Inhibitor of NF-κB kinase epsilon (IKBKE) expression compared in tumor and adjacent nontumor tissues.

Table 2 Correlation of IKBKE expression with clinicopathological parameters

Characteristic	IKBKE low expressiona	IKBKE high expressiona	p-value
Gender			0.122
Male	33	62
Female	12	11
Age			0.57
<60.5 years	21	38
≥60.5 years	24	35
Tumor location			0.601
Cervical/upper	7	8
Middle	26	40
Lower	12	25
Tumor length			0.544
<3.84 cm	26	38
≥3.84 cm	19	35
T stage			0.071
1 and 2	21	22
3 and 4	24	51
Differentiation grade			0.045
Well	16	16
Middle	13	38
Poor	16	19
LN metastasis			0.129
Negative	31	40
Positive	14	33
Positive LN			0.313
0	31	40
1	8	13
2	3	8
≥3	3	12
pTNM stage			0.023
I	12	6
II	20	37
III	13	30
Recurrence			0.059
No	24	26
Yes	21	47
Tumor thrombus			0.648
No	44	69
Yes	1	4

Notes: Values in bold signify p<0.05, considered significant.

a The proportion of IKBKE-expressing cells that exceeded 25% was grouped into high expression, and if not, then low expression.

Abbreviations: IKBKE, inhibitor of NF-κB kinase epsilon; T, tumor; LN, lymph node; pTNM, pathological tumor node metastasis.

Figure 3 Kaplan–Meier analysis of inhibitor of NF-κB kinase epsilon (IKBKE) expression in 118 cases with esophageal squamous cell carcinoma. IKBKE expression was significantly associated with decreased disease-free survival (A) and overall survival (B).

Abbreviation: Cum, cumulative.

Table 3 Univariate analysis of prognostic factors in ESCC with respect to DFS and OS

Univariate analysis	Disease-free survival		Overall survival
	HR (95% CI)	p-value	OS 95% CI	p-value
Gender	1.270 (0.715–2.257)	0.415	1.311 (0.718–2.395)	0.378
Age	0.868 (0.539–1.399)	0.562	1.032 (0.616–1.727)	0.906
Location
Upper	Ref	0.148	Ref	0.278
Middle	1.992 (0.963–4.118)	0.063	1.863 (0.845–4.107)	0.123
Low	1.128 (0.647–1.966)	0.671	1.136 (0.623–2.07)	0.678
Length	1.196 (0.743–1.928)	0.461	1.484 (0.886–2.486)	0.133
Differentiation grade
High	Ref	0.396	Ref	0.333
Middle	0.662 (0.341–1.284)	0.222	0.637 (0.328–1.236)	0.182
Low	0.974 (0.562–1.690)	0.926	0.971 (0.560–1.684)	0.916
T stage (1, 2 vs 3, 4)	1.736 (1.034–2.914)	0.037	2.526 (1.380–4.622)	0.003
Lymph nodes	2.438 (1.509–3.938)	<0.001	2.861 (1.697–4.823)	<0.001
pTNM (I, II vs III, IV)	2.288 (1.416–3.697)	0.001	2.650 (1.576–4.456)	<0.001
IKBKE expression	1.804 (1.076–3.027)	0.023	2.118 (1.189–3.773)	0.009

Note: Values in bold signify p<0.05, considered significant.

Abbreviations: CI, confidence interval; ESCC, esophageal squamous cell carcinoma; DFS, disease-free survival; HR, hazard ratio; OS, overall survival; Ref, reference; T, tumor; pTNM, pathological tumor node metastasis; IKBKE, inhibitor of NF-κB kinase epsilon.

Table 4 Multivariate analysis of prognostic factors in ESCC with respect to DFS and OS

Multivariate analysis	Disease-free survival			Overall survival
	HR	95% CI	p-value	HR	95%CI	p-value
Gender
Male vs female	1.562	0.827–2.953	0.17	1.701	0.874–3.311	0.118
Age
<61.1 vs ≥61.1	0.963	0.559–1.660	0.893	1.366	0.765–2.438	0.292
Tumor location
Upper	Ref	Ref	0.243			0.337
Middle	1.939	0.891–4.216	0.095	1.909	0.808–4.511	0.141
Lower	1.358	0.741–2.940	0.322	1.282	0.652–2.522	0.472
T
1, 2 vs 3, 4	1.362	0.753–2.462	0.307	2.05	0.998–4.215	0.051
Differentiation grade
Well	Ref	Ref	0.869			0.573
Middle	0.943	0.447–1.990	0.879	0.653	0.279–1.525	0.325
Poor	0.855	0.470–1.554	0.607	0.777	0.415–1.454	0.43
LN-M
Negative vs positive	1.533	0.686–3.429	0.289	1.635	0.644–4.153	0.301
pTNM
I, II vs III, IV	1.576	0.686–3.622	0.283	1.467	0.551–3.905	0.443
IKBKE
Low vs high	1.777	1.034–3.054	0.037	2.078	1.138–3.796	0.017

Note: Values in bold signify p<0.05, considered significant.

Abbreviations: CI, confidence interval; HR, hazard ratio; ESCC, esophageal squamous cell carcinoma; DFS, disease-free survival; OS, overall survival; Ref, reference; T, tumor; LN-M, lymph node metastasis; pTNM, pathological tumor node metastasis; IKBKE, inhibitor of NF-κB kinase epsilon.

Data availability

There are no additional unpublished data. Some original data are private. Please contact the authors with data requests if necessary.