Abstract P3-09-01: Higher Serum miR-21 Expression Correlates with Higher Levels of VEGF and bFGF in Patients with Metastatic Breast Cancer
Bibliographic record
Abstract
Abstract Background MicroRNAs (miRNAs) play an important role in the regulation of tumorigenesis and metastatic process. MiR-21 is an oncomiR that is overexpressed by breast cancer tumor tissue and is associated with high tumor grade and negative hormone receptor status. MiR-21 can control angiogenesis by regulating vascular endothelial growth factor (VEGF) as well as the expression and secretion of basic fibroblast growth factor (bFGF). MiR-19a is a member of the miR-17-92 family that was shown to suppress breast cancer cell proliferation. As angiogenesis factors act as attractants of circulating tumor cells (CTCs), a strong predictor of overall survival in metastatic breast cancer (MBC), we investigated the relationship between CTC count, levels of VEGF and bFGF, and the expression of miR-21 and miR-19a in sera of MBC patients. Methods RNA was extracted from sera collected from 33 MBC patients and 10 healthy donors (HD) using Total RNA purification Kit (Norgene Biotek Corporation, ON, Canada). The expression levels of miR-21, miR-19a and miR-192 were evaluated in triplicate by qRT-PCR using the TaqMan MicroRNA Assay (Applied Biosystems, Foster City, CA). Mir-192 was used to normalize the expression levels of miR-21 and miR-19a. The fold-change values were calculated using 2-DCt, where DCt= mean CTtarget-miRNA - mean CTmiR-192. CTCs were detected by CellSearch System (Veridex LLC, Warren, NJ). Serum VEGF and bFGF were determined using a multiplex bead assay (Millipore, Billerica, MA). Mann-Whitney U test was used to compare the miRNAs expression level between MBC patients and HD. Spearman's correlation was used to determine the association between the expression of miRNAs and growth factors. Results There was a significantly higher median level of miR-21 in MBC patients compared with HD (22.8 versus 7.2, P=0.003), while the expression level of miR-19a was similar for both groups. On average, the relative abundance of miR-21 in sera (ratio of MBC versus HD) is 3.1-fold overexpression. Furthermore, levels of miR-21 was positively correlated with the serum levels of VEGF (Spearman Rho= 0.364; P= 0.038) and bFGF (Spearman Rho= 0.367; P = 0.036). CTCs were detected in 23 patients, ranged from 1 to 134 per 7.5 mL of peripheral blood. Patients with no CTCs had a significantly higher median level of miR-19a than patients with no CTC (6.5 vs 2.8, P =0.047). Conclusion Our results support the notion that miR-21 overexpression may play a role in angiogenesis and metastasis by upregulating VEGF and bFGF in MBC. Undetectable CTC count may be related to overexpression of miR-19a, an epigenetic suppressor of breast tumor proliferation. Whereas overexpression of miR-19a may limit the tumor cells from entering the peripheral circulation, increasing miR-21 in the serum could accelerate the disease progression by promoting angiogenesis in MBC patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-09-01.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".