Associations of serum levels of microRNA-371a-3p (M371) with risk factors for progression in nonseminomatous testicular germ cell tumours clinical stage 1

Abstract

Purpose Lymphovascular invasion (LV1) and presence of > 50% embryonal carcinoma (> 50% EC) represent risk factors for progression in patients with clinical stage 1 (CS1) nonseminomatous (NS) testicular germ cell tumours. As serum levels of microRNA-371a-3p (M371) are capable of detecting small amounts of GCT, we evaluated if LV1 and > 50% EC are associated with M371 levels. Methods M371 serum levels were measured postoperatively in 153 NS CS1 patients and both pre- and postoperatively in 131 patients. We registered the following factors: age, tumour size, LV status, > 50% EC, teratoma in primary, preoperative elevation of classical tumour markers. M371 expression was compared among subgroups. The ability of M371 to predict LV1 was calculated by receiver operating characteristics (ROC) curves. Multiple regression analysis was used to look for associations of M371 levels with other factors. Results Postoperatively elevated M371 levels were found in 29.4% of the patients, but were neither associated with LV status nor with > 50% EC. Likewise, relative decrease of M371 was not associated. ROC analysis of postoperative M371 levels revealed an AUC of 0.5 for the ability to predict LV1 while preoperative M371 had an AUC of 0.732. Multiple regression analysis revealed significant associations of preoperative M371 levels with LV status (p = 0.003), tumour size (p = 0.001), > 50% EC (p = 0.004), and teratoma component (p = 0.045). Conclusion Postoperatively elevated M371 levels are not associated with risk factors for progression in NS CS1 patients. However, the significant association of preoperative M371 expression with LV1 deserves further evaluation.

miRNAs for testicular germ cell tumours: Contemporary indications for diagnosis, surveillance and follow‐up

“…In Dieckmann's large prospective study, relatively few tumours <10 mm were included. 29 Nevertheless, while the sensitivity of miR-371a-3p remained high for those patients with NSGCTs <10 mm, it dropped to 60% for seminomas <10 mm. Radtke et al examined 27 patients with GCNIS only and found that only half (51.9%) had miR-371a-3p elevations in a seemingly 'dose-dependent' manner with highest levels among those with bilateral GCNIS.…”

“…In a similar study, Dieckmann et al . showed that in 18 CS II and in nine CS III patients, miR‐371a‐3p levels dropped to zero after chemotherapy, in all but two (7%) patients 29 …”

“…One question that remains unanswered is: Can miRNAs predict the presence of small amounts of cancer (e.g., small testis masses) or pre‐invasive lesions such as Germ cell neoplasia in situ (GCNIS)? In Dieckmann's large prospective study, relatively few tumours <10 mm were included 29 . Nevertheless, while the sensitivity of miR‐371a‐3p remained high for those patients with NSGCTs <10 mm, it dropped to 60% for seminomas <10 mm.…”

MiRNA biomarkers in cancers of the male reproductive system: Are we approaching clinical application?

“…In 2022 Dieckmann et al. found a significant association between preoperative miR‐371a‐3p levels and classical histopathological risk factors of relapse (vascular invasion and >50% embryonal carcinoma) in serum of 131 patients 107 . Also, Fankhauser et al.…”

Special Issue on Testis Cancer

“…In this special issue, many of the above-mentioned prerequisites to treat patients suffering from germ cell tumors with cutting-edge knowledge and technology are presented by international experts in the field. The modern diagnostic work-up as presented by Zengerling [ 1 ], Belge [ 2 ], and Brandt [ 3 ] et al will soon include not only magnetic resonance imaging to avoid diagnostic toxicity in young ages, but will also include new tumor markers, like microRNA371a-3p, for better non-invasive staging. The consequence of this more precise staging possibilities may be the broader indication for local and less traumatic treatment options like robotic RPLND and resection of small seminoma metastases as presented by Hamilton [ 4 ] and Daneshmand et al[ 5 ].…”