Viable germ cell tumor and teratoma can be distinguished from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens by a combination of microRNA-371a-3p and 375-5p

Autor: Tim Nestler, Lara Kremer, Melanie von Brandenstein, Barbara Koeditz, Pia Paffenholz, Martin Hellmich, David Pfister, Axel Heidenreich
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:421-421
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2022.40.6_suppl.421
Popis: 421 Background: Our objective was to identify a combination of microRNAs (miRNA) to differentiate between viable tumor (V) or teratoma (T) and necrosis/fibrosis (N) in pcRPLND specimens of metastatic nonseminomatous germ cell tumor (NSGCT) patients with residual masses ≥1cm after chemotherapy. Our hypothesis is that a biomarker guided therapy could reduce overtreatment with pcRPLND in patients with only N. Methods: Forty-eight patients were identified, n = 16 each with T/V/N. Representative regions of T/V/N were microdissected, subsequently total RNA was isolated and miRNA expression was analyzed for miR-371a-3p, 375-3p, and 375-5p using qPCR. ROC analysis was performed for each miRNA and for all combinations in order to determine the discriminatory capacity of V and T vs. N. Results: For the group comparisons of V vs. N miR-371a-3p achieved the highest fold change (FC) of 31.1 (p = 0.023) while for T vs. N miR-375-5p performed best (FC 64,2; p < 0.001). Likewise, the most accurate AUC for V was 0.75 using miR-371a-3p, for T 0.80 using miR-375-5p. Combining the best performing miRNAs for V and T resulted in an AUC of 0.94 with a sensitivity of 93.75, specificity of 93.75, PPV of 96.8 and NPV of 83.3. Conclusions: In pcRPLND tissue samples V and T could be distinguished from necrosis/fibrosis by combining miR-371a-3p and miR-375-5p with great accuracy. This combination of miRNAs might serve as new biomarker in the future, in order to spare miRNA-negative patients from pcRPLND. However, further studies analyzing patient’s serum are needed to confirm the clinical impact of these biomarkers.
Databáze: OpenAIRE