Analysis of differential expression proteins of small cell lung cancer and matched normal lung tissues by 2-DE and MALDI-TOF-MS

Objective: To investigate the pathogenesis of small cell lung cancer (SCLC) and screen biomarkers for early diagnosis of this disease by analyzing differentially expressed proteins between SCLCs and matched normal lung tissues using comparative proteomic methods. Methods: Six sequential patients suffering from SCLC were included in this study. The totally soluble proteins were separated by two dimensional gel electrophoresis (2-DE) and differentially expressed proteins in the protein profiling were analyzed and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Proteins were identified by consulting NCBI or SWISS-PORT database with Mascot software. Results: Each gel obtaining about 800 protein spots were seen. The spots in the normal tissues and tumor tissues were matched with an average matching rate of 78.2% and 75.5%, respectively. Fourteen most prominent protein spots were selected for further MALDI-TOF-MS analysis, thirteen protein spots yielded peptide mass fingerprintings ( PMFs) , and eleven candidate proteins were identified and further classified into 6 categories according to their functions: 1 proteins associated with ubiquitin-proteasome pathway (UPP): proteasome subunit alpha type 3, proteasome subunit beta type 2 and prpteasome subunit beta type 5; 2 free radical metabolism/anti-oxidant: Mn-superoxide dismutase (Mn-SOD), catalase (CAT) and flavin reductase (FR); 3 cytoskeleton: tropomyosin-3 (Tpm-3); 4 protein associated with energy metabolism: thioredoxin peroxidase 1 (TPXD1); 5 molecular chaperones; prohibitin (PHB) and endoplasmic reticulum protein ER29 (Erp29); 6 others; alpha soluble NSF attachment protein (alpha-SNAP). Compared with those of the normal tissues, expression levels of proteins including Mn-SOD, CAT, PHP, ERp29, TXP and FR were upregulated, whereas expression levels of. proteins including Tpm-3 and alpha-SNAP were down-regulated in the tumor tissues. Conclusion Eleven proteins were identified by comparative proteome analysis. Most of them are associated with genesis and development of SCLC and some may serve as potential biomarkers for early detection and targets to SCLC therapy.