Circulating MicroRNAs, the Next-Generation Serum Biomarkers in Testicular Germ Cell Tumours: A Systematic Review
Why this work is in the frame
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Bibliographic record
Abstract
CONTEXT: Clinical management of testicular germ cell tumours (GCTs) is hampered by low sensitivity and specificity of the biomarkers currently in use. Circulating microRNAs (miRs) might offer the potential to address areas of unmet clinical need. OBJECTIVE: To systematically evaluate the evidence for clinical applications of serum levels of miR302/367 and miR371-3 in adult testicular GCTs in terms of primary diagnosis, various clinical scenarios, and the costs of clinical implementation. EVIDENCE ACQUISITION: We performed a critical review of PubMed/Medline, Embase and the Cochrane Library in January 2021 in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. EVIDENCE SYNTHESIS: Thirty-one manuscripts addressed miR performance and potential clinical use in testicular GCT. Of these, 23 evaluated the utility in primary diagnosis, seven in early-stage disease, and 13 in metastatic disease, and two addressed the costs of clinical implementation. Of the various miRs studied, miR-371a-3p appears the most useful and potentially the only one that needs to be assayed, with an area under the receiver operating characteristic curve >0.90, sensitivity of 89-96%, and specificity of >90% for both seminoma and nonseminoma, surpassing the classic serum tumour markers. The miRs studied to date are not elevated in cases with teratoma only. Levels of miR-371a-3p correlate with primary tumour mass, clinical stage, and International Germ Cell Cancer Collaborative Group risk groups. Serial measurements mirror treatment efficacy in all clinical stages. CONCLUSIONS: Circulating miRNA levels, particularly of miR-371a-3p, have potential for incorporation in clinical practice and may aid in clinical decision-making in various clinical scenarios in GCT. PATIENT SUMMARY: We analysed the current evidence on the usefulness of blood levels of molecules called microRNAs in the management of testicular tumours. The microRNA-371a-3p molecule has better sensitivity and specificity than the markers currently being measured. This new biomarker may soon have a place in clinical practice.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it