Testing for α-fetoprotein (AFP), β-human chorionic gonadotropin (β-HCG), and lactate dehydrogenase (LDH) in blood is essential for diagnosis, staging, and monitoring of testicular germ cell tumors (GCTs). Unfortunately, these biomarkers have low overall sensitivity and are inconsistently expressed across different GCT subtypes. Several small studies have demonstrated that serum levels of microRNA (miRNA)-371a-3p (commonly called the M371 test) as measured by quantitative polymerase chain reaction (PCR) have higher sensitivity and specificity than classic biomarkers for testicular GCTs and are applicable to both seminoma and nonseminoma. A recent prospective, multicenter study sought to evaluate the utility of the M371 test in a large and representative patient population to more thoroughly quantify the specificity, sensitivity, and accuracy of this test compared to classic markers.
Serum samples from 616 patients with testicular GCTs and 258 male controls were included in this analysis. For the primary diagnosis of GCT, the M371 test was found to have a sensitivity of 90.1%, a specificity of 94.0%, and a positive predictive value of 97.2%. When compared to classic markers of testicular GCTs, the M371 test was more sensitive than any of the three markers alone or in combination.
Level of miRNA expression correlated with tumor burden and could be used to accurately assess disease stage. Median expression of miRNA levels was significantly higher in the entire GCT group than in healthy controls, and patients with clinical stage I tumors had significantly lower miRNA levels than patients with higher stage tumors (P<.001). Paired measurements before and after orchiectomy in 424 patients revealed a significant drop in miRNA levels following treatment. Similarly, serial measurements during chemotherapy in 118 patients revealed a significant decrease in miRNA levels following the first treatment cycle. Upon relapse, patients were found to have an increase in serum miRNA levels.
The authors concluded that the M371 test is superior to classic markers of testicular GCT, with greater sensitivity and specificity and wider applicability. It represents a new, more effective biomarker for GCT diagnosis and staging and can simplify the clinical algorithm of GCT management, although further validation is needed. Importantly, while this test is accurate for both seminoma and nonseminoma, it cannot be used in patients with teratoma, as miRNA expression in this subtype is too low for accurate detection.