Hyaluronidase-1 (Hyal-1) Is Differentially Expressed in Epithelial Ovarian Cancer of Distinct Histopathological Subtypes.
Bibliographic record
Abstract
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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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 | 0.000 |
| 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".