Hyaluronidase-1 (Hyal-1) Is Differentially Expressed in Epithelial Ovarian Cancer of Distinct Histopathological Subtypes.
Notice bibliographique
Résumé
Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic cancer in most Western countries. Because of its asymptomatic growth and the lack of effective screening methods, about 70% of all cases are diagnosed in an advanced stage. Although most of the patients respond to chemotherapy initially, recurrence rate is very high resulting in poor prognosis. Furthermore, EOCs are morphologically heterogeneous, and different histopathological subtypes have distinct molecular characteristics and diverse response to treatment. In the present work we investigated the expression pattern of hyaluronidase-1 (Hyal-1) in different histopathological EOC subtypes as well as in EOC cell lines. The HYAL1 gene (together with those of HYAL2 and HYAL3) is located on the short arm of chromosome 3 (3p), a region described to contain tumour suppressor genes implicated in lung and ovarian cancer pathogenesis. However, levels of both Hyal-1 and its substrate, hyaluronic acid (hyaluronan), have also been reported to be increased in bladder, prostate and head and neck cancers, and to be implicated in tumor progression and metastasis. However, up to date, no studies have been conducted to analyze the transcriptional status of this enzyme and its role in EOC. Herein, quantitative RT-PCR was performed in ovarian tumor samples classified as borderline, serous, endometrioid, mucinous or clear cell. Distinct grade and stage were also attributed according to the International Federation of Gynecology and Obstetrics (FIGO) criteria. Cell lines derived from different EOC subtypes or from normal ovarian epithelial cells (NOSE) were also included in these analyses. Our results show that Hyal-1 expression was significantly increased in clear cell and mucinous EOC samples when compared to borderline tumors. In contrast, lower levels of Hyal-1 expression were observed in serous samples, and no difference was observed between endometrioid and borderline tumors. Accordingly, higher mRNA expression levels and higher enzymatic activity were observed in EOC cell lines derived from clear cell tumors. Cell lines derived from serous tumors had no detectable enzymatic activity and low levels of mRNA expression. However, treatment of one of these cell lines with 5-Azacytidine (DNA methyltransferase inhibitor) restored its Hyal-1 expression and activity, indicating that transcription repression through epigenetic regulation is occurring in serous EOCs. No correlation could be made between Hyal-1 expression and ovarian tumor grade or stage. In conclusion, our results show that Hyal-1 is differentially expressed in distinct EOC subtypes, with high expression levels in mucinous and clear cell carcinomas and low in serous adenocarcinoma. It is important to mention that specificity and sensitivity of the CA-125 antigen is particularly not good for these two former EOC subtypes. Therefore, Hyal-1 could be a potential marker for these tumors; however, further validation using a bigger tissue/serum sample cohort is needed. Supported by NSERC, RRCancer and FRSQ. (poster)
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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) | 0,000 | 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 tête enseignante, 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 ».