Proteoglycan-based diversification of disease outcome in head and neck cancer patients identifies NG2/CSPG4 and syndecan-2 as unique relapse and overall survival predicting factors

Table 4 Multivariate analyses of the prognostic implication of altered PG expression for the different clinical outcomes ¹ Estimated regression coefficient and confidence interval;

Prognostic indicator/PG	Estimate¹(95% CI)	SE²	p value ³	HR⁴	Clinical outcome
T classification
T2⁵	0.359 (0.153/0.565)	0.105	0,012	1.432	Loco-regional relapse
T3	1.857 (1.556/2.158)	0.153		6.404
T4	2.160 (1.956/2.364)	0.104		8.671
T3-T4 vs T1-T2	1.850 (1.691/2.009)	0.081	0.001	6.360	Loco-regional relapse
NG2/CSPG4 mRNA⁶
De novo expression vs no expression	1.911 (1.735/2.087)	0.090	0.017	6.760	Loco-regional relapse
Precancerous lesions
Presence vs Absence	1.328 (1.184/1.471)	0.073	0.005	3.773	Lymphnodal metastases
SDC2 stroma
Positive vs Negative	2.035 (1.885/2.184)	0.076	0.007	7.652	Lymphnodal metastases
SDC2 stroma
Positive vs Negative	2.160 (2.022/2.298)	0.070	0.003	8.671	Disease-related deaths
N classification
Positive vs Negative	1.477 (1.326/1.628)	0.077	0.012	4.380	Distant metastasis
N classification
Positive vs Negative	1.089 (0.967/1.211)	0.062	0.005	2.971	Disease-related deaths
N classification
Positive vs Negative	1.164 (1.003/1.325)	0.082	<0.001	3.203	Any of the clinical outcomes⁷
SDC1 mRNA
↓ /= vs ↑	−1.460 (−1.612/-1.309)	0.077	0.013	0.232	Distant metastasis
SDC1 mRNA
↓ /= vs ↑	−0.845 (−1.007/-0.684)	0.082	0.012	0.429	Any of the clinical outcomes
SDC1 mRNA up-regulation + NG2/CSPG4 mRNA de novo expression + SDC2 stroma
Single condition vs combination of all 3 conditions⁸	−1.924 (−2.088/-1.760)	0.084	0.002	0.146	Distant metastasis
	−1.302 (−1.459/-1.146)	0.080	0.004	0.272	Disease-related deaths
	−1.014 (−1.194/-0.833)	0.092	0.003	0.363	Any of the clinical outcomes

¹Estimated regression coefficient and confidence interval;
²Standard error of estimated regression coefficient;
³p value <0,05 were considered to be significant;
⁴Hazard Ratio estimated from Cox proportional hazard regression model;
⁵Compared to T1 stage;
⁶PG transcript expression (↓, down-regulated; ↑, up-regulated; =, not changed; De novo expression, de novo expressed in comparison to a healthy mucosal tissues pool that was used as sample calibrator) could be grouped according to the trend of each PG gene in relation to the clinical outcomes;
⁷Is referred to a patient that had at least one of the other outcomes within the follow-up;
⁸Refers to the comparison between a situation in which all three indicated conditions were manifested (“combination of all 3 conditions”) versus either condition alone or the combination of any two conditions;
Abbreviations: CI, Confidence Interval; HR, Hazard Ratio; SE, standard error.

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