UCHL1 expression is a poor prognostic marker in non-small cell lung cancer
Bibliographic record
Abstract
1194 Background: UCHL1 is a susceptible gene for Parkinson’s disease and has both deubiquitinase and ubiquitin ligase activities. It is commonly overexpressed in a variety of carcinomas including lung cancers. UCHL1 expression in esophageal squamous cell carcinoma and pancreatic carcinoma may also be downregulated by promoter hypermethylation. UCHL-1 is also involved in neural cell apoptosis. Materials & Methods: Quantitative-PCR (qPCR) was used to assay the expression levels of UCHL1 in two independent cohorts of non-small cell lung carcinoma (NSCLC). Cohort 1 consisted of 116 stage I-III tumors and 38 non-neoplastic tissues. The mean±95% CI of the normal was used to define the range of normal expression. Cohort 2 consisted of 172 resected NSCLC samples with similar clinical features as cohort 1. UCHL1 expression was also assessed in 10 NSCLC xenografts. Results: In cohort 1, 29.3% (34/116) overexpressed, while 3.4% (4/116) underexpressed UCHL1. Overexpression was more common in Stage I patients (32.9%) and in squamous cell carcinoma (SQCC) (51.5%). UCHL1 expression levels were also higher in smokers (p=0.012). In stage I, UCHL1 overexpression was positively correlated with differentiation grade (p=0.014) and significantly associated with shorter survival time [HR=2.57 (95%CI 1.18-5.61), p=0.017]. The survival difference remained significant even in multivariate analysis for all cases [HR=1.05 (1.02-1.08), p=0.002]. However, it was noteworthy that the 4 cases (including 2 in Stage I) that had low UCHL1 expression succumbed to NSCLC within 3 years. Cohort 2 validated findings of cohort I. Survival analysis showed a significant association between UCHL1 expression and shorter overall survival after adjustment for stage and differentiation [HR=1.25 (1.05-1.53), p=0.03]. In NSCLC xenografts, tumor growth was positively correlated with high UCHL1 expression. Interestingly, although tumors with the lowest levels of UCHL1 expression (RVH6849 and A549) grew slower than those with high expression, they also grew faster than those with intermediate expression. Moreover, the expression of UCHL1 was correlated with higher tumorigenicity in an in vitro study. Conclusion: Overexpression of UCHL1 was more frequent in early stage NSCLC and in SQCC, and was associated with shorter overall survival. However, downregulation of UCHL1 also appeared to be associated with poor prognosis.
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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 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".