The diagnosis of lung cancer is based on invasive methods and often occurs at a late stage of the disease, which explains its poor outcome. Nucleosomes are DNA fragments wrapped around histones. They can constitute a method of non-invasive and early diagnosis of lung cancer.

We investigated the clinical and statistical performance of nucleosome assay levels alone and in combination with cytokines in plasma from untreated lung cancer (LC) patients and what their discriminating power was towards chronic obstructive pulmonary disease (COPD) and healthy subjects. (H).


142 plasma samples were prospectively collected: H, n = 45; LC, n = 44 and COPD, n = 53. The circulating level of intact nucleosomes containing histone H3.1 isoform (Nu.Qª-H3.1) was tested individually and in combination with cytokines to determine their performance in the discrimination of subjects due to their underlying condition.

Then, the statistical performance of each model was tested with binary logistic regression models for the best combination of biomarkers for the following groups: cancer vs control (group A), cancer vs COPD+control (group B) and for cancer vs COPD ( group C ). The best model for each group was then applied to two independent biobank cohorts for validation.


The results for Nu.Q-H3.1 were an area under the curve (AUC) of 0.79, for groups A, B and C; sensitivity of 68%, 66% and 66% for groups A, B and C, respectively, for a specificity of 80%. For group A, the H3.1+IL-10 model achieved a sensitivity of 77% for a specificity of 80% with an AUC of 0.88 (R² = 55.8%).

For group B, the H3.1+IL-6+IL-10 model reached a sensitivity of 70% with an AUC of 0.85 (R² = 40.6%). For group C, the H3.1+IL-6+IL-10 model reached a sensitivity of 79% with an AUC of 0.85 (R² = 46.1%). The validation cohort performed similarly. The results for the 3 cohorts together were: AUC of 0.83, 0.87 and 0.90 for group A, B and C, respectively; sensitivity of 75%, 76% and 84% for group A, B and C, respectively, for a specificity of 80%.


Nucleosomes are detected in the plasma of H, LC and COPD patients. The combination with cytokines as described in these models allows a good power of discrimination between the three groups. Based on these encouraging results, we believe that more studies with a larger number of patients should be carried out to confirm and validate the usefulness of these biomarkers and models.

Determine Levels of Circulating Cell-Free Nucleosomes Containing H3.1

Active Motif’s Nu.Q™ H3.1 Assay Kit is designed for the detection of levels of circulating cell-free nucleosomes containing histone H3.1 (nucleosomes cf ) in human serum in a high-throughput format. Histone H3.1, or the canonical form of histone H3, is deposited during DNA replication and possibly also during the repair.

The study of H3.1 has identified mutations associated with cancer and different affinities for the histone acetyltransferase HAT1. To screen the H3-containing nucleosome for all variants, use our Nu.Q™ H3 assay. For convenience and more quantitative interpretation of results, the Nu.Q™ H3.1 Assay Kit also includes a recombinant nucleosome protein to use as a reference standard curve.

Why use Nu.Q™ H3.1?

  • Sensitivity: Detects circulating nucleosomes in as little as 10 µl of serum or 20 µl of plasma
  • Specificity: Nucleosome epitope-specific antibody allows detection of only intact nucleosomes
  • Quantification: Recombinant nucleosomes allow relative quantification of H3.1 nucleosome levels circulating
  • Convenience: Colorimetric assay in a simple 96-well strip format for high and low throughput
  • Fast: results can be obtained in 5 hours

Nu.Q™ H3.1