Effect of Cryptorchidism on Human Testicular Transcriptome.
Notice bibliographique
Résumé
Cryptorchidism is the most common congenital disorder in boys. One major consequence of this anomaly is male infertility due to undescended testis to which an increased risk of testicular cancer is associated. The genetic cause of cryptorchidism remains to be elucidated. The objective of this study was to compare the transcriptome of human cryptorchid testis with normal tissues. Seminoma tissues were used as a positive control of genes known to be expressed in testicular cancer. Normal tissues were obtained with collaboration of our local organ transplantation program; the five donors were from 23 to 53 years of age. Cryptorchid testes were obtained by surgical orchidectomy performed on 4 patients from 29 to 43 years of age presenting with inguinal testis. Donors of seminoma tissues were from 22 to 34 years of age and were obtained through the pathological tissues bank of our institution. Tissues samples were kept on ice and snap freeze immediately upon arrival in the research lab. Total RNA was extracted from the tissues and used to probe Affymetrix GeneChip Human Gene 1.0 ST arrays which include 28,869 genes with 764,885 distinct probes. In normal and cryptorchid tissues 2278 and 589 genes were up-regulated, respectively. As expected, transcripts known to be associated with spermatogenesis characterized the normal tissues whereas, in cryptorchid testes, transcripts of Leydig and Sertoli cells were found in higher amount. For example, PRM1 and ADAM2 transcripts associated to germ cells were in higher quantity in normal than cryptorchid testes, but CYP17A1, LHR and HSD17B3 transcripts of Leydig cells as well as GATA4, INHA and INHBA transcripts of Sertoli cells were higher in cryptorchid than normal testes. Some transcripts known to be associated with testicular cancer, such as CALR3 and PIWIL1, were up-regulated in normal tissues whereas KITLG and CCND2 were more expressed in cryptorchid testes. In seminoma tissues, PIWIL1 transcript was more expressed in cryptorchid but less in normal testicular cancer; the CALR3 and KITLG were less expressed in seminoma than in other tissues whereas the CCND2 was much more expressed in cancer tissues. Markers for testicular descent were more expressed in cryptorchids than in normal and seminomas as expected. These transcript expression patterns from the microarray results were confirmed by quantitative real-time PCR. Differences in transcriptome due to cryptorchidism will give us a clue to find the genetic cause of this disease. This work was supported by Canadian Institute of Health Research grant to Robert Sullivan. (poster)
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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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
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 ».