1911 LARGE-SCALE MITOCHONDRIAL GENOME DELETION AS AN AID FOR NEGATIVE PROSTATE BIOPSY UNCERTAINTY
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Résumé
You have accessJournal of UrologyProstate Cancer: Detection and Screening1 Apr 20111911 LARGE-SCALE MITOCHONDRIAL GENOME DELETION AS AN AID FOR NEGATIVE PROSTATE BIOPSY UNCERTAINTY Kent Froberg, Laurence Klotz, Kerry Robinson, Jennifer Creed, Brian Reguly, Cortney Powell, Daniel Klein, Andrea Maggrah, Roy Wittock, and Ryan Parr Kent FrobergKent Froberg Virginia, MN More articles by this author , Laurence KlotzLaurence Klotz Toronto, Canada More articles by this author , Kerry RobinsonKerry Robinson Thunder Bay, Canada More articles by this author , Jennifer CreedJennifer Creed Thunder Bay, Canada More articles by this author , Brian RegulyBrian Reguly Thunder Bay, Canada More articles by this author , Cortney PowellCortney Powell Thunder Bay, Canada More articles by this author , Daniel KleinDaniel Klein Thunder Bay, Canada More articles by this author , Andrea MaggrahAndrea Maggrah Thunder Bay, Canada More articles by this author , Roy WittockRoy Wittock Thunder Bay, Canada More articles by this author , and Ryan ParrRyan Parr Thunder Bay, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2049AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Numerous biological characteristics of the mitochondrial genome (mtgenome) highlight this molecule as a clinically useful “biosensor” which can discriminate between normal and malignant tissues. These characteristics include: 1) in comparison to two copies of each nuclear genome, there are 100's to 1000's of mtgenomes within a cell, increasing recoverable biomarker signal; 2) the mtgenome has an accelerated somatic mutation rate over that of the nucleus, allowing early detection of alterations indicative of malignant transformation; 3) mutations are associated with a “cancerization field effect”; 4) these mutations are often easy to screen large-scale deletions. These molecular attributes were used to further develop an assay for accurate prediction of the outcome of a relatively rapid follow-up biopsy, after an initial negative biopsy. The objective of this work was to determine the potential clinical utility of a large-scale mtgenome deletion (3.4kb) for predicting the presence/absence of tumor foci in men with an initial negative biopsy. A nested case control study was designed to mimic an actual clinical cohort, for the purposes of determining clinically significant performance metrics. METHODS The study design was a retrospective nested case controlled study on a total of 101 patients with a negative, original biopsy, which had a follow-up biopsy within 1 year of the negative procedure. Of these, 20 were malignant and the remaining 81 were negative, based on the second biopsy pathology reports. 20um sections of fixed and embedded needle cores, representing the 6 anatomical regions of the prostate, were obtained from the archived blocks of the first biopsy. A quantitative real-time PCR assay was used to determine the cycle threshold value (Ct) which provides optimum clinical information. Overall, 1000 cores from close to 400 men were used in the cumulative studies for this biomarker. RESULTS A real-time PCR Ct cutoff of 31 returned a sensitivity of 85% and a negative predictive value of 92% for predicting the results of the second biopsy. Moreover, of 22 patients with ASAP on the intial biopsy, 10 of these patients (46.5%) were malignant on the repeat biopsy. This result was predicted by the study. CONCLUSIONS A npv of 92% highlights those patients who may not require a follow-up biopsy, while a sen of 85% indicates those who may benefit from a secondary biopsy. The deletion marker is consistent with the frequency at which patients, with an initial call of ASAP, are found to have malignancy on a second biopsy. This attribute may assist in managing some patients with ASAP. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e764 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Metrics Author Information Kent Froberg Virginia, MN More articles by this author Laurence Klotz Toronto, Canada More articles by this author Kerry Robinson Thunder Bay, Canada More articles by this author Jennifer Creed Thunder Bay, Canada More articles by this author Brian Reguly Thunder Bay, Canada More articles by this author Cortney Powell Thunder Bay, Canada More articles by this author Daniel Klein Thunder Bay, Canada More articles by this author Andrea Maggrah Thunder Bay, Canada More articles by this author Roy Wittock Thunder Bay, Canada More articles by this author Ryan Parr Thunder Bay, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,005 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,002 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,066 | 0,016 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».