Proteomic analysis for detection of NSCLC: Results of ACOSOG Z4031.

7003 Background: NCI CT Screening Trial demonstrated a significant decrease in lung cancer mortality. This will dramatically increase the number of suspicious nodules discovered by CT. Unfortunately CT scans have a high false-positive rate for lung cancer requiring invasive diagnostic intervention. This study aim was to prospectively determine whether the serum proteomic profile can predict the presence of primary NSCLC in patients with CT suspicious lung lesions. METHODS: One-thousand seventy-four patients with a clinically suspicious stage I (cT1-2 N0 M0) lung lesion were enrolled in Z4031 between 02/2004 and 05/2006. Fresh-frozen and FFPE tumor with pre- and post-operatively blood were collected prospectively after informed consent. Ciba Chrome Blue was used to capture low molecular weight proteins in pre-operative serum (un-digested) followed by mass analysis on a prOTOF 2000 MALDI-TOF mass spectrometer (MS) in duplicate. The spectra were normalized and the maximum and sum amplitudes within a m/z bin were used as abundance values. Features were identified by m/z values. RESULTS: 913 patients were eligible: 723 patients with NSCLC and 190 patients with benign nodules. Patients with NSCLC were older (median 67.2 yrs vs 59.7 yrs, p < 0.0001) and had larger nodules (57.9% vs. 29.3% ≥ 2.0 cm, p < 0.0001). Of patients with NSCLC, 28% were squamous, 61.3% were adenocarcinoma, and 10% were other NSCLC. 690 eligible patients had at least one analyzable spectra. The MS proteomic profiles failed to discriminate between the groups. The spectra contained only a handful of proteins per patient and bins that had statistically significant different abundance values were in the noise region of the data and did not contain proteins. CONCLUSIONS: The proteomic platform did not have sufficient sensitivity to detect low abundance proteins. Furthermore, the limit of detection for the newest MS platforms are not sufficient for discovering discriminate protein profiles due to the dynamic range of the human proteome. A targeted approach beginning with analysis of gene expression in tissue followed by confirmation of corresponding proteins in tissue, and then assessing these proteins in serum will likely be much more fruitful and is underway.

Duke Scholars

Author Thomas Anthony D'Amico Surgery, Cardiovascular and Thoracic Surgery