Abstract LB-204: Gene expression profiling of hormone-regulating pathways in tumoral and peritumoral breast tissues
Bibliographic record
Abstract
Abstract Purpose: The purpose of our investigation was to study the mRNA expression of sex-steroids pathways involved in androgen and estrogen synthesis and metabolism in tumor and surrounding peritumoral normal breast tissues. High integrity RNA was purified and specific quantitative realtime PCR assays was performed to assess expression level of thirty two genes in breast tissues from the 4 quadrants of postmenopausal mastectomy patients diagnose with breast cancer. The expression changes between tumors (n=31) and paired normal (n=86) tissues were assessed using a general linear model on log-transformed data. Results: The main pathway involved in estrogen synthesis in postmenopausal women, steroid sulfatase, was detected at lower levels in tumor tissues compared to non-malignant tissues. mRNA expression levels of aromatase converting androgen to estrogen were relatively constant between peritumoral normal and tumoral tissues while androgen conjugating enzymes leading to inactive metabolites were overexpressed in tumoral tissues (1.4-fold; P < 0.04). Expression of CYP1A1, involved in the synthesis of 2-hydroxy-catecholestrogens, was constantly detected at lower level in tumors compared to peritumoral tissues (3.7 fold; P < 0.001). However, no prominent changes for the catechol-o-methytransferase (COMT), involved in the conversion of 2-hydroxy-catecholestrogens to methoxy metabolites with cancer-protective properties, was noted. In contrast, CYP1B1 expression was enhanced by 1.7 fold in tumors (P < 0.001) suggesting a greater in situ formation of 4-hydroxy-catecholestrogens, a group of metabolites associated with DNA damage and production of redox species. Data also reveal a lower expression in tumors of the NAD(P)H quinone oxydoreductase 2 (NQO2) most active against catechol estrogens (1.8-fold; P=0.04), while expression of NQO1 remained unchanged. These observations were further enhanced in estrogen receptor positive tumors. Conclusion: Our data add to the emerging evidence of an imbalance in the production of androgen, estrogen and their metabolites in breast tumors, preferentially leading to the accumulation of carcinogenic metabolites while decreasing protective metabolites in neoplastic tissue compared to normal tissue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-204.
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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 | 0.001 |
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".