Expression of circulating miR375 and miR371 to differentiate teratoma and viable germ cell tumor in patients with post-chemotherapy residual disease.
Bibliographic record
Abstract
414 Background: Viable germ cell tumors (vGCT) express high levels of certain circulating microRNAs, including miR-371a-3p (miR371) that has shown high specificity and sensitivity. However, neither tissue nor serum/plasma from patients with only teratoma are miR371 positive. miR375 is overexpressed in teratoma tissue, but detectability in blood is unknown. Methods: miR371 and miR375 expression was analyzed in 100 patients with various stages and histology of GCT. miR375 expression in teratoma was validated in patients with post-chemotherapy pathologically confirmed teratoma (PCPCT). The miRNAs expression was assessed by RT-PCR and quantified by ΔΔCT method. The optimal cut-off for miR375 expression was estimated by Youden index ( > 20). Spike-in cel-miR-39-3p, miR-451 and miR-30b-5p were used as internal controls. Sensitivity, specificity, AUC of the ROC of miR375 in detecting teratoma was analyzed. Results: In the discovery cohort miR371 and miR375 were measured in 62 pts: 27 CSI NED, 15 chemo-naïve metastatic seminoma and 20 with PCPCT. miR375 was over-expressed in pts with teratoma compared to CSI and seminoma pts (p = 0.002), while miR371 was expressed in the seminoma pts and undetectable in the PCPCT and CSI pts (p < 0.001). In the post-chemotherapy setting, 38 pts were analyzed: 21 PCPCT, 6 vGCT and 11 complete remission (CR). Also in this cohort, miR375 was over-expressed in pts with teratoma compared to the pts presenting vGCT and post-chemotherapy CR (p = 0.01), while miR371 was detectable only in the pts with vGCT (p < 0.001). Overall, sensitivity and specificity of miR375 in identifying teratoma were 78% and 80%, respectively; the AUC was 0.7 (95% CI: 0.5490-0.8186; p < 0.01). Conclusions: Pts with residual post-chemotherapy teratoma present higher plasma levels of miR375 compared to pts with vGCT in whom miR375 is low but miR371 is expressed at high levels. The simultaneous evaluation of miR371 and miR375 may be clinically useful to predict the histology of the GCT components in pts with post-chemotherapy residual disease to inform the best therapeutic options (surgery or chemotherapy). Further validation within larger studies is warranted.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".