Patients undergoing a biopsy of an indeterminate lung nodule by surgical excision, bronchoscopic biopsy or Interventional Radiology directed biopsy

Patients with known non-small cell lung cancer who will have surgical resection for treatment

Healthy volunteers with a) no current diagnosis of cancer; b) no history of cancer over the last 5 years; and c) no existing known benign lung disease that is currently requiring treatment with medication.

Patients with the following categories of benign lung disease:

• COPD/emphysema
• Granulomatous infection
• Interstitial lung disease including pulmonary fibrosis and interstitial lung disease.

10 cc of blood is collected at one time point, which is prior to biopsy procedure

The patients with indeterminate nodules will be used to separately estimate the sensitivity (in those with lung cancer) and specificity (in those without lung cancer). At least 35 patients with lung cancer will provide an estimate of the standard error of the sensitivity < 0.09. Specificity will also be assessed in the normal controls (healthy volunteer cohort) using exact binomial confidence intervals.

To determine the correlation between the longitudinal marker levels and time to progression, to allow adjustment for relevant clinical characteristics.

Correlations between change in the methylation results and response to therapy using radiographic findings (response, stable disease, progression) at 6 months post-baseline time point will be analyzed using a multinomial regression model.

Specificity will be assessed in the normal controls (healthy volunteer cohort) using exact binomial confidence intervals.

Thirty-five patients with benign lung disease will provide an estimate of the standard error of the specificity <0.09. Assuming a specificity value of 0.91 (32 negative/35 total), the exact 95% confidence interval is (0.77, 0.98). The specificity will be estimated separately, with an exact 95% confidence interval, for each of the benign lung disease subtypes as an exploratory analysis.