Serum Levels of MicroRNA-371a-3p (M371) Can Predict Absence or Presence of Vital Disease in Residual Masses After Chemotherapy of Metastatic Seminoma

Abstract

BackgroundRadiological evaluation of postchemotherapy residual masses of metastatic seminoma is characterized by poor diagnostic accuracy. Serum levels of microRNA-371a-3p (M371) involve high specificity and sensitivity for the primary diagnosis of seminoma. We evaluated if M371 levels can indicate the presence of vital disease in postchemotherapy residual masses in patients with metastatic seminoma.MethodsTwenty-three seminoma patients (median age 52 years) with residual masses had posttreatment measurements of serum M371 levels (group A), fourteen of whom had measurements also beforehand. The posttreatment results were compared with the clinical outcome during follow-up. Eleven patients with complete remission after treatment of metastatic seminoma (group B) and 33 men with non-malignant testicular diseases (group C) served as controls. M371 serum levels were measured by quantitative real-time PCR using miR-30b-5p as endogenous control. An evaluation was performed with descriptive statistical methods.ResultsTwenty-two patients of Group A had uneventful follow-up so far, twenty-one of whom had M371 level <5, and one other had a mildly elevated level below relative quantity (RQ) = 10. One patient with a level of RQ = 26.2 rapidly progressed. The median posttreatment M371 level of the non-progressing patients of group A is not significantly different from the median level of the control group with complete remission (B). Before treatment, the median M371 levels in groups A and B were 507.6 and 143.9, respectively. In both groups, significant drops in M371 levels resulted from treatment.ConclusionNormal M371 serum levels at the time of completion of treatment of metastatic seminoma indicate the absence of vital seminoma in residual masses, while elevated levels >RQ = 10 predict the presence of disease. The optimal timing of M371 measurement after chemotherapy and the appropriate cutoff level still need to be determined. Based on the present results, measuring serum M371 levels involves the potential of a novel tool for assessing postchemotherapy residual masses of metastatic seminoma.

Testicular neoplasms: the interrelationships of serum levels of microRNA-371a-3p (M371) and classical tumor markers with histology, clinical staging, and age—a statistical analysis

“…In the present study, the value of RQ = 5 was considered as ULN by default. As shown in a recent study on residual masses subsequent to chemotherapy in seminoma, some patients without active disease had values slightly above the RQ = 5 threshold (Dieckmann et al 2022b ). Thus, it is currently unclear, if the ULN of 5 of the M371 test is uniformly appropriate.…”

Evaluation of miR‐371a‐3p to predict viable germ cell tumor in patients with pure seminoma receiving retroperitoneal lymph node dissection

“…In the PC setting, miR‐371a‐3p also appears to have promising performance characteristics 12 . Recent reports have also indicated miR‐371a‐3p to predict viable disease in cases of PC metastic seminoma 13 …”

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

“…110 miR-371a-3p may also be useful in the assessment of post-chemotherapy residual masses of metastatic seminomas. 90 Using 52 serum samples from 10 patients, miR-371a-3p levels showed to be 13.65-fold higher in patients with proven disease recurrence, when compared with patients without evidence of disease. 89…”

“…Also, a study with 109 TGCT patients showed that higher levels of these miRNAs at the start of chemotherapy were related to worse clinical outcome and could be useful in early diagnosis of relapses 110 . miR‐371a‐3p may also be useful in the assessment of post‐chemotherapy residual masses of metastatic seminomas 90 . Using 52 serum samples from 10 patients, miR‐371a‐3p levels showed to be 13.65‐fold higher in patients with proven disease recurrence, when compared with patients without evidence of disease 89 …”

“…74,82,84,85 This versatile miRNA is informative in samples at diagnosis, but also during follow-up, detecting residual disease, correlating with tumour burden and monitoring response to therapy. 81,82,[86][87][88][89][90] There is a current interest to include miR-371a-3p as part of the surveillance strategy for TGCT patients after definitive treatment. Hence, it is important to standardize internationally the miRNA-based diagnostic pipeline and introduce miR-371a-3p in the clinical practice.…”