A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours

Murray, Matthew J.; Bell, Emma; Raby, Katie L.; Rijlaarsdam, Martin A.; Gillis, Ad J. M.; Looijenga, Leendert H. J.; Brown, Helen; Destenaves, Benoit; Nicholson, James C.; Coleman, Nicholas

doi:10.1038/bjc.2015.429

Cited by 130 publications

(178 citation statements)

References 32 publications

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“…All of the candidate miRs are located in the clusters miR-371-3 and miR 302/367 on closely related chromosomal regions [30] and accordingly, the miRs of these 2 clusters are biologically interrelated [22]. The expression of these 2 clusters represents an embryonic pattern of miRs expression.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA miR-371a-3p - A Novel Serum Biomarker of Testicular Germ Cell Tumors: Evidence for Specificity from Measurements in Testicular Vein Blood and in Neoplastic Hydrocele Fluid

Dieckmann

Spiekermann²,

Balks³

et al. 2016

Urol Int

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Background: microRNAs (miRs)-371-3 are suggested to be novel biomarkers of germ cell tumors (GCTs), but their specificity is unresolved. We aimed at clarifying the origin of miR 371a-3p by measuring this miR in peripheral vein blood, and in fluids present in the vicinity of GCTs. Methods: miR-371a-3p levels were measured by quantitative PCR in 9 tumor surrounding hydroceles and in cubital vein blood (CVB) and testicular vein blood (TVB) of 64 GCT patients, 51 with clinical stage (CS) 1, 13 with CS2-3. Thirty three CS1 cases had also postoperative CVB measurement. TVB miR levels were compared with those of CVB. Associations with clinical factors were analyzed statistically. Results: TVB miR levels were 294-fold, 80-fold and 4.6-fold higher than those in CVB of CS1 patients, CS2-3 patients and controls, respectively. Neoplastic hydrocele fluid comprised of very high miR levels. In CS1, miR levels dropped to normal postoperatively. Statistically, CVB miR levels are significantly associated with tumor size (p = 0.0211) and testis length (p = 0.0493). TVB miR levels are associated with testis length (p = 0.0129). Conclusions: This study provides evidence for the origin of circulating miR 371a-3p molecules from GCT cells. miR-371a-3p represents a specific serum biomarker for germ cell cancer.

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Section: Methodsmentioning

confidence: 99%

MicroRNA miR-371a-3p - A Novel Serum Biomarker of Testicular Germ Cell Tumors: Evidence for Specificity from Measurements in Testicular Vein Blood and in Neoplastic Hydrocele Fluid

Dieckmann

Spiekermann²,

Balks³

et al. 2016

Urol Int

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“…Recently, serum levels of microRNAs (miRs) of the clusters miR-371-3 and miR-302/367 have been suggested as novel biomarkers of GCT [5-9]. Among the candidate miRs, miR-371a-3p proved to be the most promising marker with a sensitivity of 88.7–90% and a specificity of 86–93.4% [10-13]. However, before the implementation of this marker in clinical practice, validation of its usefulness in a larger international patient cohort is required [14, 15].…”

Section: Introductionmentioning

confidence: 99%

The Novel Biomarker of Germ Cell Tumours, Micro-RNA-371a-3p, Has a Very Rapid Decay in Patients with Clinical Stage 1

et al. 2018

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Background: Accumulating evidence suggests serum levels of microRNA (miR)-371a-3p to be a novel tumour marker of testicular germ cell tumours (GCTs). Presently, there is only limited information regarding the velocity of decline of serum levels in response to treatment. Patients and Methods: Twenty-four patients with testicular GCT (20 seminoma, 4 nonseminoma, median age 40 years) with clinical stage 1 had measurements of serum levels of miR-371a-3p preoperatively and repeatedly on the following 3 days. Three had additional tests done within 24 h after surgery. Measurement results were analysed using descriptive statistical methods. Results: Serum levels dropped to 2.62, 1.27, and 0.47% of the preoperative level within 1, 2, and 3 days, respectively. The computed half-life amounts to 3.7–7 h. The velocity of decay is significantly associated with tumour size. Conclusions: Serum-levels of miR-371a-3p have a short half-life of less than 12 h. The rapid decay after treatment represents a valuable feature confirming the usefulness of miR-371a-3p as a valuable serum biomarker of GCT.

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“…MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant germcell tumours (GCTs) (Murray et al, 2016). Some of these miRNAs demonstrate an elevation in serum levels at diagnosis.…”

Section: Introductionmentioning

confidence: 99%

“…A forceful technical pipeline has been developed to quantify these miRNAs in serum and cerebrospinal fluid (CSF). The pipeline was used in samples from a cohort of entirely paediatric patients with gonadal and extra gonadal malignant GCTs, related with suitable tumour and non-tumour control groups (Murray et al, 2016). A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early recognition of decline of a testicular mixed malignant GCT; and (iii) Identified intracranial malignant GCT distinctly from intracranial non-GCT tumours using CSF and serum samples.…”

Section: Introductionmentioning

confidence: 99%

“…A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early recognition of decline of a testicular mixed malignant GCT; and (iii) Identified intracranial malignant GCT distinctly from intracranial non-GCT tumours using CSF and serum samples. It is concluded that the pipeline theoretically potentials to progress clinical controlling of both paediatric and adult malignant GCTs (Murray et al, 2016). Kirby et al (2016) suggested that use of bio-informatics incorporation of mRNA and microRNA arrays produces confirmable mRNA-microRNA pairs that are accompanying insulin resistance, and can be confirmed in vitro.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

miRNA in Cancer Pathology

Alakeel¹,

Al-Doori

2017

JMBR

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MicroRNA/miRNA refers to types of RNA which are non-coding; they are21 to 25 nucleotides in length. In most cases, at particular nucleotide locations, they relate to one or more mRNAs. Deadenylation, cleavage, and alternative procedures of translation's suppression are the means by which miRNA disturb gene repression. Recent investigations seem to propose that miRNAs are involved in many cell procedures and for this they became perfect targets for usage in healing purposes. Various miRNAs are involved in the development of human vascular diseases, due to their function in modulating vascular cell proliferation, differentiation, migration and apoptosis via their targeted genes. Since vascular diseases are multifactorial and complex, numerous genes may be involved in their progression and regulation. Therefore, miRNAs can also have multiple gene targets, and in some instances, one gene can be modulated by various miRNAs. As of now, more than 800 human microRNAs have been identified using miBase, and work is still being conducted to search for and characterize new miRNAs. With rigorous clinical and fundamental studies, a clear understanding of how miRNAs function, in addition to the ways they can be used as biomarkers and targets for cancer and cardiovascular illnesses, will progress.

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A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours

Cited by 130 publications

References 32 publications

MicroRNA miR-371a-3p - A Novel Serum Biomarker of Testicular Germ Cell Tumors: Evidence for Specificity from Measurements in Testicular Vein Blood and in Neoplastic Hydrocele Fluid

MicroRNA miR-371a-3p - A Novel Serum Biomarker of Testicular Germ Cell Tumors: Evidence for Specificity from Measurements in Testicular Vein Blood and in Neoplastic Hydrocele Fluid

The Novel Biomarker of Germ Cell Tumours, Micro-RNA-371a-3p, Has a Very Rapid Decay in Patients with Clinical Stage 1

miRNA in Cancer Pathology

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