Combination of low plasma stromal cell-derived factor-1 and phosphorylated-CXCR4: independent prognostic marker for breast cancer.
Bibliographic record
Abstract
Abstract Abstract #1069 Background: Stromal cell-derived factor (SDF)-1, a chemoattractant cytokine, has been shown to be overexpressed in those organs to which breast cancer metastasizes, and serves to home in cancer cells which express its receptor, CXCR4. We have previously reported the role of low plasma SDF-1 levels as a host-derived marker predictive of distant metastasis. Low plasma SDF-1 levels are predictive of the formation of distant metastases independently of tumor production of SDF-1. In order to further characterize this cohort of patients with an innate susceptibility for poorer prognosis, we combined low plasma SDF-1 levels with tumor-derived markers. CXCR4 has been shown to be an independent prognostic marker, however it is plausible that activated CXCR4, or phosphorylated (p)-CXCR4 may be able to better discriminate metastatic risk. We hypothesized that the prognostic value of low plasma SDF-1 would be particularly informative in patients with tumors having high CXCR4 or p-CXCR4 expression. Materials and Methods: Using the same cohort of patients in whom we previously measured plasma SDF-1 levels, we built a tissue microarray containing paraffin-embedded tissue blocks of the primary tumor for 237 patients. There were 212 patients for whom plasma and tissue blocks were both available. Plasma SDF-1 levels were previously measured using an ELISA, and tumor protein expression was detected using immunohistochemistry. Survival analysis was calculated using cox regression analysis. Results: We found that tumor p-CXCR4 was a stronger prognostic marker than CXCR4. Patients with high expression of p-CXCR4 demonstrated a 4-fold higher rate of mortality (hazard ratio (HR) 3.95, 95% confidence interval (CI), 1.55-10.03; P=0.004) in comparison to patients who highly expressed CXCR4 (HR, 3.20; 95% CI, 1.09-9.37; P=0.03) in univariate analysis. In the subset of patients for whom plasma and tissue were both available, we confirmed the poor prognostic value of low plasma SDF-1 (HR for breast cancer-specific survival, 3.59; 95% CI, 1.33-9.74; P=0.01), and high p-CXCR4 (HR, 3.98; 95% CI, 1.57-10.13; P=0.004). There appeared to be an enhancing effect of the combination of low plasma SDF-1 and high p-CXCR4 upon prognostic significance (HR, 5.96; 95% CI, (2.57-13.81); P<0.001). This remained significant with multivariate analysis (HR, 3.78; 95% CI, (1.31-10.94); P=0.01). Discussion: We report here for the first time the prognostic value of phosphorylated-CXCR4 in breast cancer, and its superiority over CXCR4 expression. Furthermore, the combination of p-CXCR4 and low-plasma SDF-1 levels was determined to be an independent prognostic marker, stronger than either factor alone, suggesting that low plasma SDF-1 may especially favor the metastatic process in patients with tumors containing its activated CXCR4 receptor. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1069.
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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 | 0.000 | 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) | 0.003 | 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".