Hypoxia-regulated gene expression and prognosis in loco-regional gastroesophageal cancer

Figures & data

Table I. Pretreatment patient and tumor characteristics.

Characteristic	ESCC (n = 56) No. (%)	EGJ/GC (n = 39) No. (%)
Histology
Squamous cell carcinoma	52 (93)	0 (0)
Adenocarcinomas	0 (0)	32 (82)
Other carcinomas	4 (7)	7 (18)
Sex
Male	42 (75)	33 (85)
Female	14 (25)	6 (15)
Age, years
Median	63	62
Range	45–76	32–78
WHO performance status score (PS)*
PS 0	22 (39)	28 (72)
PS 1	33 (59)	10 (26)
PS 2	1 (2)	1 (2)
Tumor length (endoscopy, CT or MRI)†
Median (mm)	50	50
Range	20–140	20–100
Clinical T stage (cT)
TX	4 (7)	11 (28)
T1	1 (2)	0 (0)
T2	6 (11)	15 (39)
T3	42 (75)	11 (28)
T4	3 (5)	2 (5)
Clinical N-stage (cN)
NX	0 (0)	3 (8)
N0	11 (20)	7 (18)
N1	45 (80)	29 (74)
Clinical M stage (cM)
MX	3 (5)	2 (5)
M0	52 (93)	37 (95)
M1	1 (2)	0 (0)

*WHO performance status scores on a scale from 0 to 5, with higher numbers

indicating poorer performance status.

†ESCC: n = 53, EGJ/GC: n = 29.

Figure 1. Cluster analysis of the 15 hypoxia-induced genes. (A) Unsupervised cluster analysis of 89 patients. Red colour corresponds to a high gene expression level and green colour corresponds to a low gene expression level. (B) Supervised cluster analysis of patients with ESCC according to ranking (n = 51).

Figure 2. (A) Kaplan-Meier estimates of overall survival and (B) disease-specific survival among patients with a more hypoxic genotype and a less hypoxic genotype based on the 15 hypoxia-induced genes.

Table II. Possible prognostic factors and relative risk.

	ESCC		EGJ/GC
Prognostic factors	HR (95% CI)	p-value	HR (95% CI)	p-value
Univariate analysis
Risk of death from any cause
Age (median)	1.47 (0.69–3.15)	0.32	1.97 (0.77–5.00)	0.16
Gender (male vs. female)	1.19 (0.48–2.96)	0.70	0.69 (0.23–2.12)	0.52
Tumor classification (T3–4 vs. T1–2)	4.35 (0.59–32.24)	0.15	1.31 (0.46–3.75)	0.61
Nodal classification (N1 vs. N0)	1.04 (0.40–2.77)	0.92	1.20 (0.35–4.20)	0.77
Treatment response (CR vs. non-CR)*	0.50 (0.21–1.20)	0.12
Hypoxic status (less vs. more)^†	0.48 (0.21–1.07)	0.07
Risk of disease-specific death
Age (median)	1.08 (0.44–2.67)	0.86	1.55 (0.54–4.43)	0.41
Gender (male vs. female)	0.96 (0.35–2.66)	0.94	1.17 (0.26–5.26)	0.83
Tumor classification (T3–4 vs. T1–2)^‡			1.08 (0.33–3.57)	0.89
Nodal classification (N1 vs. N0)	2.02 (0.47–8.73)	0.35	1.41 (0.31–6.37)	0.66
Treatment response (CR vs. non-CR)*	0.17 (0.04–0.73)	0.02
Hypoxic status (less vs. more)^†	0.48 (0.18–1.24)	0.13
Multivariate analysis
Risk of death from any cause
Age (median)	1.77 (0.72–4.34)	0.21	7.94 (1.89–33.38)	0.01
Gender (male vs. female)	2.12 (0.68–6.62)	0.20	4.29 (0.50–36.96)	0.19
Tumor classification (T3–4 vs. T1–2)^‡			2.00 (0.62–6.43)	0.25
Nodal classification (N1 vs. N0)	0.93 (0.19–4.50)	0.93	0.33 (0.07–1.57)	0.16
Treatment response (CR vs. non-CR)*	0.50 (0.17–1.45)	0.20
Hypoxic status (less vs. more)^†	0.46 (0.18–1.19)	0.11
Risk of disease-specific death
Age (median)	0.96 (0.34–2.71)	0.94	4.79 (1.09–21.09)	0.04
Gender (male vs. female)^§	1.67 (0.51–5.46)	0.40
Tumor classification (T3–4 vs. T1–2)^‡			1.73 (0.48–6.21)	0.40
Nodal classification (N1 vs. N0)	1.62 (0.19–13.53)	0.66	0.57 (0.10–3.33)	0.53
Treatment response (CR vs. non-CR)*	0.21 (0.05–0.95)	0.04
Hypoxic status (less vs. more)^†	0.51 (0.17–1.50)	0.22

*No patients with CR in the EGJ/GC group; ^†Analysis was not performed in the EGJ/GC group; ^‡No events in the T1-T2 group of ESCC patients; ^§No events in the group of females in the EGJ/GC group.