ABSTRACT
Blood plasma proteomes obtained from 77 lung squamous cell carcinoma (LSCC) patients (Stages I-III) and 67 healthy controls (all males) were analyzed by using the label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the search of potential cancer biomarkers. All plasma samples were depleted of 14 highly-abundant plasma proteins by immune-affinity column chromatography before LC-MS/MS. We identified and quantified 809 differential proteins with molecular weights from 6.4 kDa to 3900 kDa using a label-free method. Three hundred and sixty four proteins were identified in all three groups. Changes in levels of an expression of blood plasma proteins associated with LSCC were discovered. Among them, 43 proteins were overexpressed and 39 proteins were down-regulated by more than two-fold between the plasmas of lung cancer patients and healthy men. We focused our attention on proteins whose expression levels increased from control to early stage and then to advanced stage tumor. Each of the 43 unique overexpressed proteins was classified according to its cellular localization, biological processes, molecular function and classes. Many of these proteins are involved in biological pathways pertinent to tumor progression and metastasis and some of these deregulated proteins may be useful clinical markers.
Subject(s)
Biomarkers, Tumor/chemistry , Biomarkers, Tumor/genetics , Blood Proteins/chemistry , Blood Proteins/genetics , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/genetics , Lung Neoplasms/chemistry , Lung Neoplasms/genetics , Proteome/genetics , Aged , Chromatography, High Pressure Liquid , Databases, Protein , Down-Regulation , Humans , Middle Aged , Molecular Weight , Neoplasm Metastasis , Neoplasm Staging , Protein Hydrolysates/chemistry , Tandem Mass Spectrometry , Trypsin/chemistryABSTRACT
This single-arm, multicenter, phase II study examined the objective response rate and toxicity after neoadjuvant chemotherapy with gemcitabine and cisplatin in patients with stage IB-IIIA non-small cell lung cancer. Treatment consisted of three 21-day cycles of gemcitabine (1000 mg/m(2)) on days 1 and 8 and cisplatin (75 mg/m(2)) on day 1 of each cycle. Surgery was performed 4-5 weeks after day 1 of the last cycle of study therapy. A total of 52 patients from five investigative sites in Russia were enrolled in the study, of which 50 (96.2%) received study therapy. Of the 49 patients who were evaluable for response, six (12.2%) had a complete response and 16 (32.7%) had a partial response, resulting in an overall response rate of 44.9%. Disease progression occurred in four out of the 49 (8.2%) patients. Radical tumor resection was performed in 38 out of the 49 (77.6%) patients. A total of 41 patients were assessed for a pathological complete response, of which four (9.8%) patients had pathological complete tumor regression. Postsurgical restaging was performed in 36 out of the 41 (87.8%) patients. Tumor downstaging occurred in 16 out of the 36 (44.4%) patients. Grade 3/4 neutropenia and thrombocytopenia were experienced by 28.0%/6.0% patients and 6.0%/2.0% patients, respectively. Grade 3 anemia occurred in 4.0% of the patients. Nonhematological toxicity was mild. Overall mortality was 30.0% (15 out of 50 patients), predominantly from progressive disease. The 1-year overall survival rate was 74.4% (95% confidence interval: 61.3-87.6%). Neoadjuvant chemotherapy with gemcitabine and cisplatin showed a good safety profile with an encouraging possibility of curative surgery in patients with early-stage non-small cell lung cancer.
