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Purpose: Proteomic analysis of tumor and lung parenchymal tissue may throw important light on the pathogenesis of nonsmoking-related adenocarcinoma in Hong Kong Chinese women. Methods: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to profile lung tissue samples to generate phenomic fingerprints. Applying in duplicate on immobilized metal affinity capture proteinchip array using automated sample handling robotics, SELDI patterns were generated from 29 primary lung tumors (21 adenocarcinoma, 8 squamous cell carcinoma) with matched noncancer specimens. Data were analyzed by the CiphergenExpress biomarker analysis system. Results: In the comparison of cancer and noncancer tissues, 22 proteins/peptides were found to have significant different profiles (p < 0.05). The areas under receiver operating characteristic curve (AUC) for the top ten biomarkers range from 0.78 to 0.88. Although the association between smoking and lung cancer has been well established, a higher proportion of the female patientswith adenocarcinoma are nonsmokers in Hong Kong. Comparing the cancer and noncancer tissues of these particular patients (n = 8), 16 significant proteins/peptides were discovered, with a high AUC ranging from 0.84 to 0.98 for the top ten biomarkers. When further analysis was conducted to distinguish the adenocarcinoma with smoking history (n = 12) from those without smoking history (n = 9), 15 proteins/peptides were found to have significant differentiating values. The AUC for the top ten biomarkers range from 0.80 to 0.96. Conclusions: In this discovery-phase study, SELDI-TOF MS has successfully analyzed tumor tissue from patients with lung cancer and discovered protein patterns that could discriminate diseased from healthy tissue. The biomarker candidates that are highly specific to nonsmoking adenocarcinoma, especially for female patients, may yield new insights about molecular pathways that are altered in this particular adenocarcinoma in Hong Kong. Further characterization of the potential biomarkers found in this study is in progress.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA