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Objective:To search the specific serum proteins in tumor-like polypoid lesions of the gallbladder(PLG)patients. Methods:Surface enhanced laser desorption/ionization time of flight mass spectrometry(SELDI-TOF-MS)technique and WCX Magnetic Beads were used to detect the serum proteomic fingerprint of 23 patients with tumor-like PLG,21 patients with non tumor-like PLG and 26 normal persons.Biomarker Wizard and Biomarker Patterns Software were used in combination to analyze the data. Results:In the preliminary screening,22 representative specific proteins for tumor-like PLG were found.Seven specific proteins showed increased expression and 15 specific proteins showed decreased expression in the tumor-like PLG patients.Three specific proteins are selected for the diagnosis of the tumor-like PLG.. Conclusion:SELDI-TOF-MS technique can be used to select specific proteins for tumor-like PLG patients,which may be useful for the diagnosis of the tumor-like PLG and the differential diagnosis with the non tumor-like PLG.