SELDI may facilitate the management of germ cell tumor

Abstract

4580 Background: Germ cell tumors (GCT) are highly curable. Nevertheless, some patients relapse and develop chemotherapy-resistant GCT. Surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry (SELDI) can determine protein mass profiles based on the biological and electrophysical properties of proteins. SELDI has been successfully applied to diagnose cancer, identify tumor markers, and determine sensitivity and response to chemotherapy. In this study, we performed a SELDI analysis to differentiate curable versus persistent GCT after chemotherapy, and to identify those patterns that are associated with chemoresistance. Our long-term goal is to identify markers that are associated with GCT and chemoresistance. Methods: SELDI analysis with serum samples was performed to determine proteomic patterns. Serum samples were collected from patients who remained disease-free over 2 years (NED). The samples were also collected from patients with newly diagnosed (most likely to be chemosensitive) and recurrent (resistant to first-line chemotherapy) GCT, both before and after chemotherapy. The proteomic patterns are correlated with clinical outcomes (i.e. NED vs. active disease, chemosensitive vs. resistant). In the long term, a prediction system will be generated based on the correlation between proteomic patterns and clinical outcomes. An independent test cohort will be used to validate the prediction system. Results: SELDI analysis has been performed in 24 NED serum samples, 20 samples with newly diagnosed GCT and 11 samples with recurrent GCT following initial chemotherapy. The SELDI mass spectral patterns were essentially homogenous within each group, but significantly different between these three groups. Seven and 10 protein peaks, having a p-value of less than 0.05, were identified to distinguish between the active GCT and NED groups; and the newly diagnosed from recurrent GCT groups, respectively. The proteomic patterns will be correlated with clinical outcomes (cure vs. relapse, chemosensitivity vs. resistance). Conclusions: SELDI may be able to distinguish between patients with active GCT and those who are free of the disease. The technique can readily identify chemosensitive versus chemoresistant GCT. No significant financial relationships to disclose.