Myelin-associated proteins are potential diagnostic markers in patients with primary brain tumour

Figures & data

Table 1. Nogo-A, MAG, and OMgp concentrations in patients with brain tumours compared to non-tumoural individuals.

	Total brain tumour	Astrocytic brain tumour	Meningeal tumour	Non-tumoural group
	Nogo-A (pg/mL)
CSF	418.00 (249.00–1964.00)^b	462.00 (352.00–2998.00)^a,b	234.00 (98.50–646.50)^b	6,550.00 (3,627.00–10,017.00)
Serum	0.00 (0.00–0.00)	0.00 (0.00–0.00)	0.00 (0.00–0.00)	0.00 (0.00–0.00)
	MAG (ng/mL)
CSF	7.43 (4.15–12.99)	7.12 (2.77–16.58)	7.43 (6.22–9.15)	9.86 (6.67–13.92)
Serum	0.00 (0.00–2.65)^b	0.00 (0.00–4.18)^b	0.00 (0.00–2.61)^b	6.95 (3.03–14.19)
	OMgp (ng/mL)
CSF	0.00 (0.00–0.09)	0.00 (0.00–0.80)	0.00 (0.00–0.00)	0.00 (0.00–0.00)
		AR = 23.1	AR = 18.1	AR = 16.0
Serum	0.00 (0.00–0.10)^b	0.00 (0.00–0.46)	0.00 (0.00–0.00)^b	0.24 (0.00–1.49)
		AR = 20.3	AR = 14.1	AR = 27.4

Results are presented as median with 25th and 75th percentiles. For patients with astrocytic brain tumour, patients with meningeal brain tumour, and control subjects we also calculated the OMgp average rank (AR), which better characterizes concentration changes between these groups.

CSF: cerebrospinal fluid.

a Statistically significant when compared to the meningeal group.

^bStatistically significant vs. non-tumoural group.

Figure 1. (A) CSF Nogo-A dot plots for the astrocytic and meningeal brain tumour groups and non-tumoural individuals. (B) Serum MAG dot plots for the astrocytic and meningeal brain tumour groups and non-tumoural individuals. (C) Serum OMgp dot plots for the astrocytic and meningeal brain tumour groups and non-tumoural individuals. p < .05 is considered to be statistically relevant. CSF: cerebrospinal fluid.

Table 2. Logistic regression analysis.

Covariates	OR	95% CI	p Value
Univariate logistic regression analysis
Sex	3.958	1.27–12.29	.017
CSF Nogo-A (pg/mL)	0.999^a	0.99–0.99	<.001
WBC (×10^3/µL)	1.446	1.17–1.78	.001
K^+ (mmol/L)	3.709	1.09–12.57	.035
Glucose (mg/dL)	1.022^b	1.00–1.04	.034
Urea (mg/dL)	1.090	1.04–1.14	.001
Multivariate logistic regression analysis
CSF Nogo-A (pg/mL)	0.998^a	0.99–0.99	.005
K^+ (mmol/L)	17.264	1.21–246.73	.036
Urea (mg/dL)	1.228	1.05–1.44	.010
Creatinine (mg/dL)	0.001	0.00–0.70	.039

OR, odds ratio; CI, confidence interval.

a OR interpreted by intervals of 100 units.

b OR interpreted by intervals of 10 units.

Conversion factor conventional to SI unit: WBC [10⁹/L] – 1.0, glucose [mmol/L] – 0.0555, urea [mmol/L] – 0.357, creatinine [µmol/L] – 88.402.

Figure 2. (A) ROC curves for CSF Nogo-A (AUC ± SE = 0.909 ± 0.033, p < .001; YI = 0.65; SE = 65%; SP = 100%; AC = 77%; PPV = 100%; NPV = 59%) and serum MAG (AUC ± SE = 0.797 ± 0.079, p < .001; YI = 0.57; SE = 77%; SP = 80%; AC = 78%; PPV = 92%; NPV = 53%) for differentiating the combined brain tumour groups from non-tumoural individuals. (B) ROC curves for CSF Nogo-A (AUC ± SE = 0.871 ± 0.045, p < .001; YI = 0.56; SE = 73%; SP = 83%; AC = 77%; PPV = 86%; NPV = 69%) and serum MAG (AUC ± SE = 0.770 ± 0.090, p = .003; YI = 0.60; SE = 70%; SP = 90%; AC = 77%; PPV = 93%; NPV = 60%) for differentiating the astrocytic brain tumour group from non-tumoural individuals. C: ROC curves for CSF Nogo-A (AUC ± SE = 0.987 ± 0.013, p < .001; YI = 0.88; SE = 88%; SP = 100%; AC = 95%; PPV = 100%; NPV = 92%) and serum MAG (AUC ± SE = 0.850 ± 0.089, p < .001; YI = 0.60; SE = 80%; SP = 80%; AC = 80%; PPV = 80%; NPV = 80%) for differentiating the meningeal brain tumour group from non-tumoural individuals. ROC: receiver operating characteristic; CSF: cerebrospinal fluid; AUC: area under the ROC curve; SE: standard error; Cut-off: optimal cut-off based on the highest Youden Index; YI: Youden Index; SE: sensitivity; SP: specificity; AC: diagnostic accuracy; PPV: positive predictive value; NPV: negative predictive value.

Figure 3. (A) Kaplan–Meier survival analysis for the total study group. Males and females were analyzed separately. Based on CSF Nogo-A median concentrations, males/females were divided into those with CSF Nogo-A^Low (≤median; Me = 1356 pg/mL) and those with CSF Nogo-A^High (>median). (B) Kaplan–Meier survival analysis for the whole study group. Based on CSF MAG median concentrations, patients were divided into those with CSF MAG^Low (≤median; Me = 7.43 ng/mL) and those with CSF MAG^High (>median). (C) Kaplan–Meier survival analysis for the whole study group. Based on serum MAG median concentrations, patients were divided into those with serum MAG^Low (≤median; Me = 0.00 ng/mL) and those with serum MAG^High (>median). CSF, cerebrospinal fluid.

Data availability statement

The datasets generated and/or analyzed during the current study are not publicly available, but are available from the corresponding author (OMK-L) on a request.