Analysis Of Serum Protein Patterns In Esophageal Cancer Patients Of The Uighur In Xinjiang By SELDI-TOF-MS

Objective: Most patients of esophageal carcinoma(EC) have developed to advanced stages at the time of diagnosis and more than a half have either unresectable tumors or radiographically visible metastases. The 5-year survival rate was 30%-48% for all patients of EC who were after radical excision. The 5-year survival rate was less than 10% for all patients of EC. But a 5-year survival rate of 84.1% and a 10-year survival rate of 73% would be achieved if the patients were diagnosed in early stage. However, early detection of cancer truly depends on the discovery of specific and sensitive molecular biomarkers. Promising diagnostic patterns have recently been reported using surface enhanced laser desorption/ ionization-time of flight-mass spectrometry technology (SELDI-TOF-MS). SELDI-TOF-MS is an affinity-based MS method in which proteins are selectively adsorbed to a chemically modified surface and impurities are removed by washing with buffer. By combining different ProteinChipR array surfaces and wash conditions, SELDI allows on-chip protein rapture and micropurifica- tion, thereby permitting high-throughput protein expression analysis of a large number of clinical samples. So the aim of this study is to analyze the alterations of serum protein patterns in esophageal cancer patients of the Uighur in Xinjiang by SELDI-TOF-MS (surface-enhanced laser desorption/ionization time of flight mass spectrometry), screen and build diagnosis model of esophageal cancer of Uighur in Xinjiang and investigate its clinical value. Materials and methods: One hundred and fifty-two serum samples from patients with different stage and grade EC and 49 ones from age- and sex-matched healthy individuals were analyzed by CM10 ProteinChip under defined binding and washing conditions. All samples were analyzed and the diagnostic model was established by using Cancer Institute of Zhejiang University- ProteinChip Data Analysis System (ZUCI-PDAS) .The diagnostic model was evaluated and validated by leave one cross validation. Results: Two hundred and seventy-seven protein peaks were detected at molecular range of 2 000-20 000Da in the training set(152 EC and 49 controls) ,among which 135 ones were significantly different between EC and controls of Uighur in Xinjiang(z<0.01).A diagnostic pattern consisting of seven protein peaks(5667.5944,5915.5052,5875.9478,5645.0247,6059.3041,6102.8642,5690.7198 m/z) was established with a sensitivity of 99.34% (151/152) and a specificity of 95.92% (47/49). The diagnostic pattern was evaluated and validated by leave one cross validation. Its sensitivity was 96.05% (146/152) and specificity was 83.67%(41/49).Conclusion: Using SELDI-TOF technology, we have discovered a candidate EC pattern consisting of 7 peaks and build the diagnostic model. The model can do the best in discriminating esophageal cancer of Uighur from controls. It provides a new approach for diagnosing and screening esophageal cancer of Uighur in Xinjiang. Combined use of bioinformatics tools and proteomic profiling provides an effective approach for screening potential serum tumor markers.