Work

Plasma miR-371a-3p for detection of non-teratomatous viable germ cell tumor in testicular cancer

Year: 2018

Type: article

Abstract: Background: Active surveillance for CSI testicular cancer is currently based on serial radiological imaging and classic tumor markers (β-HCG, AFP, LDH). The management of borderline suspicious tumor markers negative enlarging nodes and of the post-chemotherapy residual disease is challenging, and currently relies on clinical follow-up with imaging to establish patterns of growth or pathological confirmation with biopsy or retroperitoneal lymphadenectomy (RPLND). A blood-based approach to reliably identify patients with non teratoma viable GCT (NTVGCT) would be valuable. Methods: Plasma miR-371a-3p (miR371) of pts with GCT was analyzed by RT-PCR. Spike-in cel-miR-39-3p and miR-30b-5p as internal controls. miR-451a and miR-23a-3p were used as quality control for the hemolysis. The miR371 expression was used to calculate its area under the ROC curve, sensitivity and specificity in detecting viable NTGCT. Results: One hundred samples from 79 patients (44 CSI and 35 metastatic) were analyzed. Nineteen CSI pts presented suspicious enlarging nodes (≥ IIA) during surveillance and 8/19 had confirmed relapse. miR371 predicted the clinical relapse in 6/8 of pts while the 11 CSI pts with unconfirmed enlarging nodes were all negative for miR-371. miR371 was expressed in all the pre-chemotherapy metastatic pts and negative after chemotherapy (n = 25). miR371 was negative in all the pts with post-chemotherapy residual radiographic findings (n = 24). No residual NTVGCT was detected in any of these 24 pts by either pathology at resection (n = 16) or clinical follow-up (n = 8). The area under the ROC curve was 0.94, the sensitivity and specificity were 89% and 98%, respectively. The results showed a high concordance comparing 2 independent experiments conducted in house and in an outside lab (r = 0.98 and 0.87, respectively). Conclusions: Detectable circulating miR371 expression predicts the presence of NTVGCT. If validated in larger real world settings, this may result in significant change in the practice for all patients with germ cell tumors by moving it to a biological rather than radiological decision base. These encouraging findings inform upcoming North American trials for further definition of miR371 operating characteristics in GCTs. Legal entity responsible for the study: Lucia Nappi. Funding: GUMOC research grant 2017. Disclosure: All authors have declared no conflicts of interest.

Source: Annals of Oncology

DOI: 10.1093/annonc/mdy283.118