GP88/PGRN Serum Levels Are Associated with Prognosis for Oral Squamous Cell Carcinoma Patients

Thomas Greither, Tina Steiner, Matthias Bache, Ginette Serrero, Sven Otto, Helge Taubert, Alexander W Eckert, Matthias Kappler, Thomas Greither, Tina Steiner, Matthias Bache, Ginette Serrero, Sven Otto, Helge Taubert, Alexander W Eckert, Matthias Kappler

Abstract

Progranulin (PGRN)/GP88 is a growth factor that is expressed in a wide range of tumor tissues. The secreted form is involved in various biological processes including proliferation and inflammation. In several tumor types, the serum GP88 level is associated with a patient's prognosis; however, data for oral squamous cell carcinomas (OSCCs) have not yet been reported. We measured the serum GP88 levels in 96 OSCC patients by an enzyme immunosorbent assay (EIA) and correlated these data with clinicopathological parameters and patient outcomes. The GP88 levels in the serum of OSCC patients and healthy volunteers were comparable. In OSCC patients, the levels did not correlate with age, sex, or TNM status. In a Kaplan-Meier survival analysis, a serum GP88 level < 68 ng/mL was significantly associated with worsened survival (p = 0.0005, log-rank-test) as well as in uni- and multivariate Cox regression analyses (RR = 4.6 [1.6-12.9], p = 0.004 and RR = 4.2 [1.2-12.0], p = 0.008). This effect was predominant in OSCC patients older than 60.5 years (p = 0.027), while in younger patients no significant association between serum GP88 levels and prognosis could be observed. Altogether, lower serum GP88 levels are significantly associated with a worsened outcome for an OSCC and may be an interesting candidate for risk stratification during OSCC therapy.

Keywords: GP88; OSCC; prognosis; progranulin; serum.

Conflict of interest statement

GS is co-founder and CEO of A&G Pharmaceutical Inc., Columbia, Maryland, USA. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Serum GP88 level distribution in OSCC patients and healthy volunteers.
Figure 2
Figure 2
Distribution of serum GP88 levels according to (a) sex, (b) age median, (c) T stage or (d) nodal metastasis.
Figure 3
Figure 3
ROC analysis of serum GP88 levels according to overall survival of the OSCC patients used for Youden index calculation. AUC of the ROC curve was 0.684 (95% CI: 0.577–0.792), p = 0.002.
Figure 4
Figure 4
Survival analyses according to (a) Kaplan-Meier and (b) univariate Cox regression survival analyses estimating the influence of the serum GP88 level on the OSCC patients prognosis.
Figure 5
Figure 5
Multivariate Cox regression analysis modelling the survival of OSCC patients according to their serum GP88 levels.

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