Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer

Abstract

Background: In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery.

Methods: Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2).

Results: A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003).

Conclusions: Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact.

Keywords: Head and neck cancer; Osteopontin; Perioperative changes; Survival; TGFβ1.

Fig. 1

Scheme of the three patient groups treated by A) surgery, B1) definite radio-chemotherapy and B2) surgery followed by postoperative radiotherapy. Time points for blood samples are marked as T0 to T3 (T0, before surgery (group A) or before start of radiotherapy (group B1 and B2), T1, 1 day after surgery, T2, 1 week and T3, 3 to 4 weeks after surgery). S, surgery; RT, radiotherapy

Fig. 2

Box and whisker plots demonstrate the distribution plasma levels of a) OPN and b) TGFβ1 in the different patient groups and healthy controls at time point T0 before treatment. Bars indicate statistical significant differences with p < 0.05

Fig. 3

Time course of OPN plasma levels for group A with a) OPN and b) TGFβ1 (T0, before surgery, T1, 1 day after surgery, T2, 1 week and T3, 3 to 4 weeks after surgery). Bars indicate statistical significant differences with p < 0.05. c shows OPN time course for patients with OPN levels above or below median indicating that patients in both groups return to their pre-surgery status

Fig. 4

Positive correlation between TGFβ1 and OPN plasma levels at time point T0. Pearson correlation coefficient R = 0.619, p = 0.001

Fig. 5

Kaplan-Meier curves show overall survival for patients in group a (perioperative, A), group B1 (primary radiotherapy, b) and group B2 (postoperative RT, c) according to OPN at time point T0. When dichotomized by median or tertiles, patients with lower OPN had an improved overall survival. For TGFβ1 a difference in survival was seen in patients from group B1, showing a better survival for patients in the lower two tertiles (d)