MicroRNAs as Appropriate Discriminators in Non-Specific Alpha-Fetoprotein (AFP) Elevation in Testicular Germ Cell Tumor Patients

Lembeck, Anna L; Puchas, Philip; Hutterer, Georg C.; Barth, Dominik A.; Terbuch, Angelika; Bauernhofer, Thomas; Pichler, Martin

doi:10.3390/ncrna6010002

Cited by 13 publications

(10 citation statements)

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“…Since only one in two patients with precursors of TGCTs had elevated serum levels and there were also contradictory results reported from other research groups, miR-371a-3p cannot replace a biopsy to differentiate between pre-cursor lesions and TGCT, but it may help with unclear histological results [63,76]. A recently published case report suggest a discriminative power of miR-371a-3p to differentiate between unspecific AFP elevations [77].…”

Section: Mir-371a-3pmentioning

confidence: 99%

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

Regouc

Belge

Lorch

et al. 2020

Cancers

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Testicular cancer is an important disease with increasing incidence and a high burden of morbidity and mortality in young men worldwide. Histological examination of the testicular tissue after orchiectomy plays an important role alongside patient history, imaging, clinical presentation and laboratory parameters. Surgical procedures and chemotherapeutic treatment provide a high chance of cure in early stages, though some patients in advanced stages belonging to a poor risk group experience cancer-related death. Though conventional serum-based tumor markers, including α-fetoprotein (AFP), the β-subunit of human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH), are useful as prognostic and diagnostic biomarkers, unfortunately, these tumor markers only have a sensitivity of about 60%, and in pure seminoma even lower with about 20%. Therefore, the development of new tumor markers is an important and intensively ongoing issue. The analysis of epigenetic modification and non-coding RNA microRNAs (miRNAs) are carrying most promising potential as tumor markers in future. miRNAs are small RNAs secreted by testicular tumor cells and circulate and be measurable in body fluids. In recent years, miRNAs of the miR-371-373 cluster in particular have been identified as potentially superior tumor markers in testicular cancer patients. Studies showed that miR-371a-3p and miR-302/367 expression significantly differ between testicular tumors and healthy testicular tissue. Several studies including high prospective multi-center trials clearly demonstrated that these miRNAs significantly exceed the sensitivity and specificity of conventional tumor markers and may help to facilitate the diagnosis, follow-up, and early detection of recurrences in testicular cancer patients. In addition, other miRNAs such as miR-223-3p, miR-449, miR-383, miR-514a-3p, miR-199a-3p, and miR-214 will be discussed in this review. However, further studies are needed to identify the value of these novel markers in additional clinical scenarios, including the monitoring in active surveillance or after adjuvant chemotherapy, but also to show the limitations of these tumor markers. The aim of this review is to give an overview on the current knowledge regarding the relevance of non-coding miRNAs as biomarkers in testicular cancer.

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Section: Mir-371a-3pmentioning

confidence: 99%

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

Regouc

Belge

Lorch

et al. 2020

Cancers

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“…This miR, thus represents a specific tumor marker for GCTs, which is not expressed in other diseases. By contrast, the specificity of the classical tumor marker AFP is considerably hampered by its association with non-GCT related conditions, such as liver diseases [37].…”

Section: Correlation Of Mir-expression Levels In Tissue With Serum Lementioning

confidence: 99%

Graded expression of microRNA-371a-3p in tumor tissues, contralateral testes, and in serum of patients with testicular germ cell tumor

et al. 2020

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Copyright: Belge et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Background: Serum levels of microRNA-371a-3p represent a specific tumor marker of testicular germ cell tumors (GCTs) but the origin of circulating miR-371a-3p is not finally resolved. The correlation between miR-levels in tissue and serum is unclear.Results: MiR-levels in GCT tissue are 399-fold higher than in contralateral testicular tissue and 5843-fold higher than in non-testicular tissue. MiR tissue levels correlate with corresponding serum levels (r 2 = 0.181). ISH detected miR-371a-3p intracellularly in GCT cells except teratoma. A low expression was also detected in normal testicular germ cells.Conclusions: Circulating miR-371a-3p is specifically derived from GCT tissue. The miR is present in GCT cells except teratoma. A low expression is also found in normal testicular tissue but not in non-testicular tissue. MiR-371a-3p levels in tissue and serum correlate significantly. This study underscores the usefulness of serum miR-371a-3p as tumor marker of GCT.Patients and methods: Expression levels of miR-371a-3p were concurrently measured in tissues of GCT, contralateral testes (n = 38), and in serum (n = 36) with real time PCR. For control, 5 healthy testicles and 4 non-testicular tissue samples were examined. MiR-levels were compared using descriptive statistical methods. We also performed in situ hybridization (ISH) of GCT tissue with a probe specific for miR-371a-3p.

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“…Clinical management of TGCTs is extensively guided by imaging technologies e.g. computed tomography or magnetic resonance imaging and by serum levels of tumour markers alpha fetoprotein (AFP), beta Human chorionic gonadotropin (bHCG) and lactate dehydrogenase (LDH) (Albers et al 2015 ; Honecker et al 2018 ; Lembeck et al 2020 ). Unfortunately, the utility of the classical tumour markers is compromised by their low sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Serum levels of microRNA-371a-3p are not elevated in testicular tumours of non-germ cell origin

Belge

Grobelny

Radtke

et al. 2020

J Cancer Res Clin Oncol

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Purpose Serum levels of microRNA-371a-3p (M371) have been shown to be a highly sensitive and specific biomarker for testicular germ cell tumours (TGCT). Little information exists on the expression of this marker in testicular neoplasms deriving from the gonadal stroma or other structures of the gonad. This study presents an expression analysis of the novel TGCT-biomarker M371 in a large cohort of testicular non-germ cell tumours. Methods The M371 expression was measured by quantitative real time PCR in serum of 99 patients with testicular tumours of non-germ cell origin, thereof 30 patients with malignant testicular lymphomas and 61 patients with gonadal stroma tumours such as Leydig cell tumours, Sertoli cell tumours and 8 cases with miscellaneous benign testicular tumours. Their M371 levels were compared to those of 20 patients with TGCT and to 37 tumour-free male controls. Results The median expression levels of benign testicular tumours and testicular lymphoma are close to zero, thus, identical with those of controls and significantly lower than those of TGCT. In summary, this study provides further evidence for the notion that M371 is exclusively expressed by germ cell tumours and not by testicular neoplasms of the non-germ cell subtypes. Conclusion Clinically, the test might be of value in preoperative characterization of benign testicular tumours eligible for conservative surgery.

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MicroRNAs as Appropriate Discriminators in Non-Specific Alpha-Fetoprotein (AFP) Elevation in Testicular Germ Cell Tumor Patients

Cited by 13 publications

References 20 publications

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

Graded expression of microRNA-371a-3p in tumor tissues, contralateral testes, and in serum of patients with testicular germ cell tumor

Serum levels of microRNA-371a-3p are not elevated in testicular tumours of non-germ cell origin

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