Use of carbonic anhydrase IX (CAIX) expression and Von Hippel Lindau (VHL) gene mutation status to predict survival in renal cell carcinoma
Bibliographic record
Abstract
5042 Background: VHL gene mutations induce the expression of CAIX, and previous studies have shown that low CAIX results in worse prognosis for RCC. We attempt to further describe the relationship between CAIX expression, VHL gene mutations and tumor characteristics. Methods: Radical nephrectomy was performed in 100 patients at 2 centers. Genomic DNA was extracted from frozen tumor samples using the QIAmp DNA mini kit. Four amplimers covering the whole coding sequence of the VHL gene were synthesized by PCR and sequenced by Big Dye. Mutation bearing sequences were confirmed by a second round of sequencing. The monoclonal antibody M75 was used to score the expression of the CAIX protein. Life table, Kaplan-Meier and Cox regression analyses addressed RCC-specific mortality (RCC-SM). Results: VHL mutations were identified in 58 patients (58%) and CAIX tumor expression ranged from 0% to 100%. Low CAIX expression (<85%) was associated with absence of VHL mutation (p=0.02), larger tumors (p=0.002), higher T stage (p=0.007), nodal metastases (p=0.001) and higher Fuhrman grade (p=0.006). Absence of VHL mutation was associated with worse ECOG (p=0.005), higher T stage (p=0.01) and presence of nodal (p=0.03) and distant metastases (p=0.02). Categorically-coded, CAIX was a statistically significant predictor of RCC-SM (p=0.002), while VHL mutation approached statistical significance (p=0.08) and a trend was observed for worse survival when VHL was not mutated. Patients with both high CAIX and VHL mutation had better survival (95.9% 1 year and 6 year median survival) than their counterparts with low CAIX expression and absence of VHL mutation (62.9% 1 year and 1.5 year median survival) (p<0.001). In Cox regression analyses, neither CAIX (p=0.06) nor VHL (p=0.4) achieved independent predictor status, when adjusted for age, gender, TNM stage, tumor size, Fuhrman and ECOG. Conclusions: Low CAIX expression is associated with the absence of VHL mutation and aggressive tumor characteristics, and is a statistically significant predictor of poor prognosis in patients with clear cell RCC. No significant financial relationships to disclose.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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".