| Esophageal carcinoma (EC) is one of the main digestive system malignant tumor. China is a country of high incidence of esophageal cancer and Esophageal squamous cell carcinoma (ESCC) accounts for about 80%of the total number. Epidemiological characteristics of esophageal cancer, the differences in ethnic distribution is one of its main features in addition to significant differences in geographical distribution. Esopha-geal cancer in Xinjiang has a significant regional and national aggregation, which suggest the incidence of esophageal cancer in Xinjiang be affected by the combined effect of environmental and genetic factors. Existing research for Uygur in Xinjiang only few studies on esophageal cancer, and insufficient information available. There is still a lack of early diagnosis of esophageal cancer. Most of the time of diagnosis of esophageal cancer patients are already in the late, their treatment is not so effective. Surgery is the main method of treatment of esophageal cancer. The leading death causes of patients with esophageal cancer after surgery are tumor recurrence and metastasis. Lymphatic metastasis (LM) is an important prognostic factor for esophageal cancer. Current problem is that we can not accurately determine the existence of LM before surgery. So it bring a certain blindness to surgery and treatment options. To improve TNM staging of patients prior to surgery, especially, to improve the accuracy of LM, show great significance for improving the treatment and improving the prognosis of patients with esophageal cancer. So far, there is no effective serum markers application found in diagnosis of esophageal cancer recurrence and metastasis in early stage. How to improve the early diagnosis of esophageal cancer and preoperative diagnostic accuracy of LM, and effective monitoring of recurrence and metastasis after treatment, especially look for convenient and effective diagnostic markers in serum, have become an important direction of clinical and basic research.Protein is the actual implementation and embodiment of those life activities. The development of cancer often have protein dynamics. Proteomics can identify cells, tissues or whole body protein, which provides a set information of protein function and mode and also reflects the genetic characteristics and the results of the impacts of external factors on inside cells. So, looking for specific and sensitive marker for preoperative staging and postoperative follow-up monitoring calls for the further explora-tion for proteome. Using differential proteomics on the expression and quantitative differences between tumor and the normal or benign lesions, and characterization of selected tumor-associated protein markers has become a research hotspot. With the rapid development of proteomics-related technologies, clinical serum proteomics become very active in the field of life sciences disciplines. From a new angle, clinical serum proteomics studies and finds tumor markers, which provides an important basis for early cancer diagnosis, prognosis and dynamic monitoring.A novel technology, surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) evared out such a new path to porteomics research on cancer. As high qunatities of data were obatined from proteomics fields, which traditonal mathematic and statistic methods can not analysis so much data efficiently. Proteins are captured by adsorption, partition, electrostatic interaction, or affinity chromatography on a solid-phase protein chip surface. The protein chip chromatographic surfaces in SELDI are uniquelydesigned to retain proteins from complex mixtures according to their specific properties. After adding a matrix solution, proteins can be ionized with a nitrogen laser and their molecular masses measured by TOF-MS. These different mass to charge ratio (M/Z) of ions in a vacuum electric field in the different lengths of time of flight, thus rendering the mass spectra to obtain a variety of protein molecular weight, abundance and other information. Compared with patients with a disease by their map information, the new disease-related proteins will be found. SELDI-TOF-MS mass spectrometry have been applied to the study biomarkers in many tumor and succeed.Application of SELDI-TOF-MS technique on different nationalities for detection of serum protein fingerprint suggest that information of all health ethnic groups is different from patients with esophageal obviously. In this study, combined clinical and pathological data, SELDI-TOF-MS technology was used for explore the differences in serum proteins between patients with esophageal cancer and the healthy person and estimated the value of diagnosis and preoperative diagnosis of LM in Uygur patient with esophageal cancer in Xinjaing.Objective:The following three aspects analyzed in this study ars to:1) Screen serum tumor biomakers and find diagnostic model of ESCC by SELDI-TOF-MS and ZUCI-Protein Chip Data Analyze System package (ZUCI-PCDAS) in Uygur in Xinjiang; 2) Screen serum tumor biomakers and find diagnostic model of LM of ESCC by SELDI-TOF-MS and PCDAS in Uygur in Xinjiang; 3) Screen serum tumor biomakers and analyze the perioperative dynamic variation of it by SELDI-TOF-MS in patients with ESCC. Methods:1) Serum samples from 42 ESCC Uygur’s patients and 22 Uygur’s healthy controls were analysed on weak cation exchange and hydrophobic surface protein chip (CM 10) using SELDI-TOF-MS technology in screen out the serum differentially expressed markers of ESCC; 2) Serum samples from 42 ESCC Uygur’s patients,21 with and 22 without intrathoracic LM, were screened were detected on weak cation exchange (CM 10) protein chip using SELDI-TOF-MS technology. The obtained protein expression profiles data were devited into two groups named as diagnostic cast, and the results were analyzed using ZUCI-PDAS software in order to screen out serum differentially proteins. 3) Preoperative and postoperative serum samples from 45 patients were detected on weak cation exchangeand hydrophobic surface protein chip (CM10) using SELDI-TOF-MS technology. Also, serum samples of 64 patients and 63 health control the results were were detected. The result of these two groups were comparative analyzed to monitering dynamic variation of biomaker. Results:1) M/Zs were significantly different between ESCC patients and controls in Uygur (P<0.05). Among them, five proteins peaks (4487.3973、15963.7368、9160.7745、5494.4509、11693.8038) were high-expressed and five(2763.4477、8712.8596、6648.88、6681.2584、8789.2461) were low-expressed in ESCC group. According to cross validation, seven proteins composed and established diagnostic model. The sensitivity and specificity of the diagnostic model were 86.05%(37/43) and 68.18%(15/22); 2) M/Zs were significantly different between ESCC patients with and without LM in Uygur (P<0.05). According to cross validation, six proteins composed and established diagnostic model. The sensitivity and specificity of the diagnostic model were 76.19%(16/21) and 77.27%(17/22) respectively; 3) There was significantly difference of serum protein profiling between preoperative and postoperative patients. Three of protein peaks in preoperative sample, which was higher in health control than preoperative patients, was lower postoperatively. Conclusion:1) The combination of Surface-enhanced laser desorption ionization time of flight mass spectrometry and bioinformatics software analysis is a effective method searching for biomarkers of esophageal squamous cell carcinoma, constitutes sensitive diagnostic model can accurately distinguish esophageal squamous cell carcinoma and healthy Uygur. The established sensitive diagnostic model can accurately distinguish esophageal squamous cell carcinoma with healthy Uygur people; 2) The serum protein patterns were significantly different among uygur patients with positive lymph node detection, lymph node-negative patients and healthy controls,5 protein peaks (M/Z%16081.0634, 16152.0842,15962.2598,2019.8519,2044.3842) of which may be important for determining prognosis; 3) The three Screened protein peaks may not be specific markers secreted by tumor, may be suppressed immune related protein in the tumor patients, or relevant indicators of nutritional status because of swallowing difficulties compared with normal. Further study of its molecular characteristics is needed. |
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