Circulating Serum miRNA (miR-367-3p, miR-371a-3p, miR-372-3p and miR-373-3p) as Biomarkers in Patients with Testicular Germ Cell Cancer

Syring, Isabella; Bartels, Joanna; Holdenrieder, Stefan; Kristiansen, Glen; Müller, Stefan; Ellinger, Jörg

doi:10.1016/j.juro.2014.07.010

Cited by 168 publications

(140 citation statements)

References 24 publications

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“…Tests targeting these specific miRNAs are currently under development. Preliminary studies have already proven great specificity (99-100%) and sensitivity of these tests for the detection of TGCT [100][101][102]. Other body fluids are also suitable for detection of miRNA released by disseminated tumours, e.g.…”

Section: Traces Of Gct In Blood: Classical Biochemical Markers and MImentioning

confidence: 99%

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

Meyts

Nielsen

Skakkebæk

et al. 2015

Folia Histochem Cytobiol.

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This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCT), with focus on the most common testicular GCT (TGCT). GCT are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic differentiation. TGCT that occur in young men are divided into two main types, seminoma and nonseminoma, both derived from a pre-invasive germ cell neoplasia in situ (GCNIS), which originates from transformed foetal gonocytes. In severely dysgenetic gonads, a GCNIS-resembling lesion is called gonadoblastoma. GCT occur rarely in young children (infantile GCT) in whom the pathogenesis is different (no GCNIS/gonadoblastoma stage) but the histopathological features are similar to the adult GCT. The rare spermatocytic tumour of older men is derived from post-pubertal spermatogonia that clonally expand due to gain-of function mutations in survival-promoting genes (e.g. FGFR3, HRAS), thus this tumour has a different expression profile than GCNIS-derived TGCT. Clinically most informative immunohistochemical markers for GCT, except teratoma, are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related factors, such as placental-like alkaline phosphatase (PLAP), OCT4 (POU5F1), NANOG, AP-2γ (TFAP2C) and LIN28, which are not expressed in normal adult germ cells. Some of these markers can also be used for immunocytochemistry to detect GCNIS or incipient tumours in semen samples. Gene expression in GCT is regulated in part by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation, except nonseminomas. In addition, a recently discovered mechanism of post-genomic gene expression regulation involves small non-coding RNAs, predominantly micro-RNA (miR). Testicular GCT display micro-RNA profiles similar to embryonic stem cells. Targeted miRNA-based blood tests for miR-371-3 and miR-367 clusters are currently under development and hold a great promise for the future. In some patients miR-based tests may be even more sensitive than the classical serum tumour markers, b-chorio-gonadotrophin (b-hCG), a-fetoprotein (AFP) and lactate dehydrogenase (LDH), which are currently used in the clinic. In summary, research advances have provided clinicians with a panel of molecular markers, which allow specific diagnosis of various subtypes of GCT and are very useful for early detection at the precursor stage and for monitoring of patients during the follow-up.

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Section: Traces Of Gct In Blood: Classical Biochemical Markers and MImentioning

confidence: 99%

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

Meyts

Nielsen

Skakkebæk

et al. 2015

Folia Histochem Cytobiol.

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“…130 Subsequently, the expression levels of these tissue-based signatures were measured in serum. [131][132][133][134][135][136] These liquid biopsy data confirmed the potential utility of miRNA measurements for discriminating patients with seminoma or those with nonseminoma from healthy control subjects. A selected set of four miRNAs (miR-371a-3p, miR-372, miR-373 and miR-367) present in the two clusters that showed the highest discriminative power for diagnosis and follow-up of cancer, combined with reference miRNAs (miR-20a and miR-93) and spike-in controls was developed as the 'targeted serum miRNA assay' (TSmiR).…”

Section: [H1] Biofluid Micrornas In Testicular Cancermentioning

confidence: 67%

“…134,136 Two independent studies, confirmed these promising results for miR-371a-3p as a biomarker for testicular cancer; however these reports only included a limited number of participants. 132,133 A simplified assay for analysing miR371a-3p without endogenous controls was recommended to reduce laboratory work, analytical time and costs. 137 Results of another study confirmed the discriminative ability of serum miR-371a-3p and miR-372 concentrations and also identified numerous novel discriminative serum miRNAs (miR-511, miR-26b, miR-769, miR23a, miR-106b, miR-365, miR-598, miR-340 and let-7a), which were identified using a high-throughput profiling system, but did not validate the results.…”

Section: [H1] Biofluid Micrornas In Testicular Cancermentioning

confidence: 99%

The translational potential of microRNAs as biofluid markers of urological tumours

et al. 2016

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“…Our own data also confirm the improved sensitivity (85%) and specificity (99%) of miR-371 when compared to AFP (14%) and HCG (37%). 9 In summary, several independent studies indicate an increase of miR-371-373 in TGCT patients irrespective of their histological subtypes and, therefore, result in a better diagnostic performance than AFP/HCG.…”

Section: Nucleic Acids Micrornamentioning

confidence: 91%

Novel tumor markers in the serum of testicular germ cell cancer patients: a review

Syring¹,

Müller²,

Ellinger³

2014

CBF

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Serum tumor markers have an important role in the management of patients with testicular cancer. They are useful for diagnosis, staging and risk assessment, follow-up, evaluation of response, and early detection of relapse. Alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are established serum markers in testicular cancer, but they have a limited sensitivity. Ongoing research may lead to the identification of novel biomarkers. Therefore, we review the experimental analyses for nucleic acids, circulating tumor cells, and proteins as potential biomarkers in the serum of testicular germ cell cancer patients.

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Circulating Serum miRNA (miR-367-3p, miR-371a-3p, miR-372-3p and miR-373-3p) as Biomarkers in Patients with Testicular Germ Cell Cancer

Abstract: miR-371a-3p allows for better identification of testicular germ cell tumor than α1-fetoprotein and human chorionic gonadotropin. It could be helpful for clinically managing testicular germ cell tumor, especially for monitoring surveillance therapy and residual disease after chemotherapy.

Cited by 168 publications

References 24 publications

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

The translational potential of microRNAs as biofluid markers of urological tumours

Novel tumor markers in the serum of testicular germ cell cancer patients: a review

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