ArticlemedRxiv : the preprint server for health sciences2026
Urinary 27-nor-5β-cholestane-3α,7α,12α,24
Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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10 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Background: Lung cancer in never-smokers is excluded from low-dose computed tomography screening because eligibility is defined by smoking history, and no non-invasive marker is available to select never-smokers for imaging. We evaluated urinary 27-nor-5β-cholestane3α,7α,12α,24 Methods: CPG was quantified by ultra-performance liquid chromatography-tandem mass spectrometry against a synthetic standard in urine from two independent case-control studies (661 cases, 690 controls). The primary analyses compared never-smoker cases directly with never-smoker controls (NCI-Maryland, 114 cases and 203 controls; Colorado, 80 cases and 108 controls) by logistic regression adjusted for age, sex and race, for all stages and by stage, pooled across studies. Survival among never-smoker cases was analyzed by Kaplan-Meier and Cox regression. Analyses of all participants and of tumor transcriptomes were secondary. Results: CPG was higher in never-smoker cases than in never-smoker controls in both studies (both P < 0.001). Adjusted odds ratios (OR) per standard deviation were near-identical across studies (1.83, 95% CI 1.32-2.54, and 1.81, 1.24-2.65; heterogeneity P = 0.96; pooled 1.82, 1.43-2.31). Elevation was present in stage I-II disease (pooled OR 1.38, 1.04-1.82) and greater in stage III-IV disease (2.27, 1.66-3.12). Single-marker discrimination was modest (area under the curve 0.63 and 0.70). High CPG was associated with shorter overall survival among never-smoker cases in NCI-Maryland independently of stage (hazard ratio 2.56, 1.58-4.14), and in the same direction in Colorado (1.63, 0.72-3.69). Among all participants, CPG was also higher in cases (pooled OR 1.61, 1.42-1.82), without effect modification by smoking, and remained associated after mutual adjustment for creatine riboside and Conclusions: Urinary CPG is reproducibly elevated in never-smokers with NSCLC compared with never-smoker controls, including in early-stage disease, in two independent studies. These phase 2 data support evaluation of CPG within multimarker panels in pre-diagnostic urine from never-smokers, a population with no current screening pathway.
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