Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (β-subunit of human chorionic gonadotropin (β-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease (p = 0.014). In contrast, miR-367 levels were not different in these patient groups (p = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials.
International journal of molecular sciences. 2018 Oct 12*** epublish ***
Angelika Terbuch, Jan B Adiprasito, Verena Stiegelbauer, Maximilian Seles, Christiane Klec, Georg P Pichler, Margit Resel, Florian Posch, Anna L Lembeck, Herbert Stöger, Joanna Szkandera, Karl Pummer, Thomas Bauernhofer, Georg C Hutterer, Armin Gerger, Michael Stotz, Martin Pichler
Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Department of Urology, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Department of Urology, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Department of Urology, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Department of Urology, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. ., Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria. .