PAX3d mRNA over 2.76 copies/μL in the bloodstream predicts cutaneous malignant melanoma relapse
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Chiara Autilio1, Carmela Paolillo1, Maria Michela Lavieri2, Krizia Pocino1, Elisa De Paolis1, Enrico Di Stasio3, Paolo Marchetti4, Cappellini Antonini Gian Carlo6 and Ettore Capoluongo1,5,7
1Institute of Clinical Biochemistry, Laboratory of Clinical Molecular Diagnostics, Fondazione Policlinico “A. Gemelli”, Catholic University of the Sacred Heart, Rome, Italy
2Unit of Dermatology, “Cristo Re” Hospital, Rome, Italy
3Laboratory of Clinical Biochemistry, Fondazione Policlinico “A. Gemelli”, Rome, Italy
4Sant’Andrea Hospital, Rome, Italy
5Laboratory of Advanced Molecular Diagnostics (DIMA), Istituto Dermopatico dell’Immacolata, Fondazione Luigi Maria Monti, IRCCS, Rome, Italy
6Oncology Unit Immacolata Dermatological Institute (IDI), Rome, Italy
7“Molipharma Srl” a Spinoff of Catholic University, Campobasso, Italy
Keywords: melanoma molecular biomarker, qRT-PCR, melanoma relapse, circulating tumor cells, PAX3
Received: June 17, 2017 Accepted: July 25, 2017 Published: August 11, 2017
Objective: The aim of this study was to evaluate if our molecular algorithm, based on tumor circulating transcripts, may predict relapse risk in cutaneous malignant melanoma (CMM).
Results: The multi-marker panel was able to differentiate patients with CMM from HC with high diagnostic sensitivity and specificity, especially for MITF-m and TGFB2 (91–100%) whose levels decreased during follow-up of recurrence-free patients, and remained stable in the case of relapse. PAX3d higher than 2.76 copies/μL emerged as a promising biomarker [specificity = 75–93% and negative predictive value = 75–98%] to stratify subjects at high risk of CMM recurrence independently of age, gender and AJCC staging [OD = 9.5(3.2–28.0), p < 0.001]. The survival analysis confirmed PAX3d performance in relapse prediction with significant differences in recurrence risk 12 months after the basal time-point (p = 0.008).
Materials and Methods: Peripheral blood was collected from 111 CMM patients and from 87 healthy controls (HC) randomly selected. Each specimen was examined by qRT-PCR analysis for the expression of 3 tumor-related transcripts (PAX3d, MITF-m and TGFB2) at diagnosis, and at the following 6 and 12 months during clinical monitoring.
Conclusions: We demonstrated the usefulness of our molecular algorithm to indirectly detect circulating melanoma cells in blood, along with PAX3d capability to assess patients’ progression and relapse prediction.
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