Serum levels of IGF-1 and IGF-BP3 are associated with event-free survival in adult Ewing sarcoma patients treated with chemotherapy

Figures & data

Figure 1 Schematic overview of the effect of EWSR1-FLI1oncoprotein on IGF-1 pathway in Ewing sarcoma cells.

Note: EWSR1-FLI1 binds the promoter region of IGF-BP3, which inhibits transcription.
Abbreviations: EWSR1-FLI1, Ewing sarcoma breakpoint region 1-Friend leukemia virus integration 1; IGF-1, insulin-like growth factor 1; IGF-BP3, insulin-like growth factor-binding protein 3; IGF-2, insulin-like growth factor 2; IGF-1R, insulin-like growth factor 1 receptor; IR-A, insulin receptor isoform A; PI3K, phosphatidylinositol- 3-kinase; AKT, protein kinase B; MAPK, mitogen-activated protein kinase.

Table 1 Patient characteristics

Patients (N=22)
Gender
Female	6 (27.3%)
Male	16 (72.7%)
Age (years)
Range	16–62
<18	3 (13.6%)
≥18–30	10 (45.5%)
≥30	9 (40.9%)
Median BMI (range), kg/m^2	22.7 (17.0–36.8)
Chemotherapy before diagnosis
Yes	1 (4.5%)
No	21 (95.5%)
Surgery before diagnosis
Yes	3 (13.6%)
No	19 (86.4%)
Extraskeletal
Yes	5 (22.7%)
No	17 (77.3%)
Metastasis
With metastasis	9 (40.9%)
Only pulmonary	4 (18.2%)
Skeletal	3 (13.6%)
Bone marrow	2 (9.1%)
Without metastasis	13 (59.1%)
Response to chemotherapy
Good	14 (63.6%)
Poor	5 (22.7%)
Not applicable	3 (13.6%)

Abbreviation: BMI, body mass index.

Figure 2 Serum levels of IGF-1, IGF-BP3, and IGF-2 at baseline and after five cycles of VIDE chemotherapy (N=13).

Abbreviations: IGF-1, insulin-like growth factor 1; IGF-BP3, insulin-like growth factor binding protein 3; IGF-2, insulin-like growth factor 2; VIDE, vincristine/ifosfamide/doxorubicin/etoposide; CI, confidence interval.

Figure 3 Kaplan–Meier curves of event-free survival (left column) and overall survival (right column) for IGF-1, IGF-BP3, and molar IGF-1 (nm/L):IGF-BP3 (nm/L) ratio levels under or above the cutoff point.

Note: P-values are given for the univariate analyses of the Cox regression analyses.
Abbreviations: IGF-1, insulin-like growth factor 1; IGF-BP3, insulin-like growth factor-binding protein 3; EFS, event-free survival; OS, overall survival.

Table 2 Univariate and multivariate Cox models of EFS for IGF-1, IGF-BP3, IGF-2, and IGF-1:IGF-BP3

	Univariate analysis			Multivariate analysis
	HR	95% CI	P-value	HR	95% CI	P-value
Metastasis at diagnosis	2.061	0.575–7.380	0.267
Age	1.021	0.973–1.071	0.396
BMI	1.158	0.998–1.343	0.053
IGF-1	0.075	0.009–0.602	0.015	0.063	0.007–0.590	0.015
IGF-BP3	0.090	0.011–0.712	0.022	0.057	0.005–0.585	0.016
IGF-2	1.809	0.451–7.254	0.403
IGF-1:IGF-BP3	0.082	0.010–0.660	0.019	0.103	0.011–0.934	0.043

Note: Bold values indicate P<0.05.

Abbreviations: EFs, event-free survival; HR, hazard ratio; IGF-1, insulin-like growth factor 1; IGF-BP3, insulin-like growth factor-binding protein 3; IGF-2, insulin-like growth factor 2; HR, hazard ratio; CI, confidence interval; BMI, body mass index.