Abstract 235P
Background
Methylated nucleosomes are reported as putative cancer biomarkers (Grolleau, 2023). ONCOPRO (NCT03787056) is a prospective case-control study led in Lyon University Hospital that collected plasma at diagnosis and along disease management of 420 patients with 16 newly cancers. Additionaly, we were authorized to assess the diagnostic and prognostic values of circulating nucleosomes in NSCLC (CSE N23-5168).
Methods
Concentrations of nucleosomes (H3K27Me3, H3K36Me3, ng/mL) were measured with Nu.Q® immunoassays (Volition SRL) in 69 plasma of NSCLC and compared to 179 healthy subjects. Their prognostic values regarding overall survival (OS) and cancer progression were assessed.
Results
H3K27Me3 and H3K26Me3 baseline concentrations were significantly higher in patients with NSCLC compared to healthy subjects (median H3K27Me3, 15.28 vs 9.76 ng/mL, P<0.0001; H3K36Me3, 15.42 vs 10.25 ng/mL, P<0.0001), independently of tumor mutational status. The diagnostic accuracy in NSCLC / control was assessed in the whole population (ROC AUC 0.67 95% CI 0.58-0.76 for H3K27Me3; ROC AUC 0.78 95% CI 0.72-0.85 for H3K36Me3). The baseline titers were higher in the palliative compared to the curative cohorts (median H3K27Me3, 18.46 vs 9.54 ng/mL; H3K36Me3, 18.88 vs 12.73 ng/mL). In patients of the palliative cohorts, high concentrations of H3K27Me3 and H3K36Me3 at diagnosis were associated with a poor OS (H3K27Me3 < or ≥ 18.46 ng/mL, median OS NR, 95% CI NR-NR vs. 10.09 months, 95% CI 7.1-NR, HR=4.86, 95% CI 1.41-16.78, p=0.012; H3K36Me3 < or ≥ 18.88 ng/mL, median OS NR, 95% CI NR-NR vs. 10.09 months, 95% CI 7.1-NR, HR=7.22, 95% CI 1.66-31.45, p=0.0084) and first progression (H3K27Me3 < or ≥ 18.46 ng/mL, HR=2.33; 95% CI = 1.13-4.81, p=0.022; H3K36Me3 < or ≥ 18.88 ng/mL, HR=2.68, 95% CI 1.29-5.55, p=0.008). Baseline titers of H3K27Me3 and H3K36Me3 were predictive of PFS at 7 months for patients in palliative cohort not treated with immunotherapy (H3K27Me3, ROC AUC = 0.81 [0.62; 1.00]; H3K36Me3, ROC AUC = 0.87 [0.71; 1.00]).
Conclusions
Baseline values of H3K36Me3 and H3K27Me3 could represent a non-invasive biomarker in NSCLC, with potential relevant prognostic tumor burden value and progression-risk value in newly diagnosed patients.
Clinical trial identification
NCT03787056 CSE N23-5168, 16/06/2023.
Legal entity responsible for the study
B. You.
Funding
Volition SRL.
Disclosure
B. You: Financial Interests, Institutional, Funding: Gilead. L.F. Payen: Financial Interests, Institutional, Sponsor/Funding: Volition; Financial Interests, Institutional, Funding: AstraZeneca. All other authors have declared no conflicts of interest.