Genetic sequence variant (GSV) in <i>TERT-CLPTM1L </i>(5p15.33 locus) and survival in platinum-treated stage-IV non-small cell lung cancer (NSCLC).
Bibliographic record
Abstract
1535 Background: Lung cancer is a leading cause of cancer-related mortality in North America. Besides tobacco smoking, inherited genetic factors can also influence the development of lung cancer. These genetic factors may lead to biologically distinct subsets of cancers that have different outcomes. We evaluated whether GSVs associated with lung cancer risk are also associated with overall survival (OS) and progress free survival (PFS) in platinum-treated stage-IV NSCLC patients. We chose this subset of patients with lung cancer because they are uniformly treated and followed up at our institute (Princess Margaret Hospital). Methods: A total of 32 candidate GSVs in 21 genes previously reported to be associated with lung cancer risk were genotyped in 188 platinum-treated NSCLC stage-IV patients. Illumina Custom GoldenGate Genotyping Panel was used for the genotyping assay platform. Multivariate Cox proportional hazard models adjusted for the potential clinical prognostic factors were generated for OS and PFS. Results: Median age is 60 yr (range: 31-81); 73% with adenocarcinoma. Median follow-up time is 27 mo; median OS is 16 mo and PFS is 8 mo. The top significant GSV was rs4975616 (g.1315660G>A) in telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) gene on chromosome 5p15.33. The adjusted hazard ratio (aHR) for OS was 0.76 (95% CI: 0.58-0.99; p=0.04) and for PFS aHR was 0.70 (95% CI: 0.55-0.90; p=0.005) for each protective allele, respectively. This GSV has previously been associated with lung cancer risk in genome-wide association study (PMID: 19654303). Conclusions: The TERT-CLPTM1L:rs4975616 GSV is not only a risk factor for lung cancer but also is associated with survival in patients with stage-IV NSCLC treated with platinum based chemotherapy. GSVs may be able to define subsets of patients with different risk and prognosis of NSCLC. Future studies should evaluate whether this GSV is predictive or prognostic.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".