Identification Of Esophageal Carcinoma Associated Proteins By Proteomics In Han, Uygur And Kazakh In Xinjiang China

Lack of obvious early symptoms, most of the patients are already in advanced stage with a poor prognosis when they are diagnosed as a esophageal carcinom (EC); and overall surgical 5 years survival rate remains poor at 28%-31.6%. However, surgical treatments for early stage EC increase 5 years survival rate up to 90%. Early diagnosis of EC still is a tickler because of unclear cause, indefinite pathogenesis and absence of sensitive effective early stage biological diagnostic criteria or method. Therefore, early detection, early diagnosis and early treatment become a study trend in this field. Especially, early detecting EC biological markers is a direction in basic and clinical research. Along with the development of proteomics cross-correlation technique, clinical serum protein proteomics become the most active branch of bioscience. Clinical serum protein proteomics reveals tumor with a new prospect, and it provides tumor markers for early diagnosis, prognosis and dynamic monitoring. Lately, surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) technology is succeed in several tumor marker studies.SELDI-TOF-MS technology requires that various protein of biological specimen (cellular fluid or body fluid) is adsorbed on protein chip by specific surface groups, and protein is resoluted into ion using optical pulse radiation. Time of flight of different ion in vacuum electric field is different, so on these grounds, mass spectrum is drawn to obtain molecular weight of protein [especially low molecular weight (<250), light concentration protein] and richness data. Target disease is compared with normal control data to detect new disease related protein.Tumor is known as genetic disease. Genetic mutation, gene deletion, gene abnormal expression play a important role in canceration. Gene function is accomplished by , encoding protein, therefore, protein is the substantial performer of vital movement. Dynamic alteration of protein induces canceration, so at present tumor is considered as disease of protein. Using the proteomics technique, analysis on the differentially expressed proteins identification, quantitation, exosyndrome of normal, benign or malignant tumors and screening of tumor correlative protein labels become a hotspot of recent research.EC is one of the most geographically and racially varied cancers. In China, it has become the most common malignancy among Kazakh people of Xinjiang Uygur Autonomous Region. The incidence rate is 155.9 per 100,000, in Tuoli county of Tacheng, but incidence rate of other ethnic groups is 22.3 per 100,000 in same area. There are certain differences of living habit among different ethnic groups, and genetic apparents are also different. Thus, the differences of serum protein profiles in different ethnic groups may provide a new serum diagnostic method for screening and ealy diagnosis of EC in Xinjiang. Objective:To screen out serum protein profiles alteration of esophageal carcinoma (EC) patients in different ethnic groups in Xinjiang (including Han, Uygur and Kazakh) using SELDI-TOF-MS technology to establish EC diagnostic cast serum markers, in order to consummate EC serum protein profiles for ealy diagnosis and prognostic monitoring. The following three aspects were analyzed in this study.1) Serum differentially expressed protein of EC patients in Xinjiang were analyzed; 2) Serum protein finger prints of Han, Uygur and Kazakh EC patients were analyzed; 3) Serum protein profiles alteration of Kazakh EC patients with or without lymph node were analyzed. Methods:1) Serum samples from 127 EC patients and 63 healthy controls were analysed on weak cation exchange (WCX2) and hydrophobic surface protein chip using SELDI-TOF-MS technology in screen out the serum differentially expressed markers of esophageal carcinoma.2) Serum protein finger prints from patients with EC (43 Han,43 Uygur and 41 Kazakh) were detected on weak cation exchange (CM10) 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) Serum samples from 21 Kazakh EC patients with lymph node positive and 20 Kazakh EC patients with lymph node negative and 20 Kazakh healthy controls were analysed on weak cation exchange (CM 10) and hydrophobic surface protein chip using SELDI-TOF-MS technology, the results were analyzed using ZUCI- Protein Chip Data Analyze System package. Results:1) M/Zs were significantly different between EC patients and controls (P<0.05) among these six (4487.750,5494.5520,15964.0660,3948.4357,8154.1979 and 8166.2978) proteins peaks were high-expressed and four (8788.6519,6682.1680,8713.6010 and 6649.6970) were low-expressed in EC group. According to cross validation, six proteins composed and established taxonomic tree model. The accuracy, sensitivity and specificity of the diagnostic model were 96.8% (184/190),97.6%(124/127) and 95.2%(60/63).2) There were significant different between Han, Uygur and Kazakh EC patients in terms of serum protein finger prints (P< 0.05) M/Z 4310.0109 proteins peaks were low-expressed in Han but high-expressed in Uygur and Kazakh patients group.3) M/Zs were significantly different between Kazakh EC patients of lymph node positive and controls (P<0.05). According to cross validation, five proteins(16086.7070.15965.2172,16159.2743,8791.8863,7995.2049) composed and established taxonomic tree model. The accuracy, sensitivity and specificity of the diagnostic model were 95.12%(39/41),90.48%(19/21) and 100%(20/20); M/Zs were significantly different between Kazakh EC patients of lymph node negative positive and controls (P<0.05). According to cross validation, three proteins(13789.3396.6899.9365. 4978.9241) composed and established taxonomic tree model. The accuracy, sensitivity and specificity of the diagnostic model were 97.50%(39/40),100%(20/20) and 95.00% (19/20); And M/Zs were significantly different between Kazakh EC patients of lymph node positive and lymph node negative group (P<0.05). which is 16081.0634,16152.0842.15962.2598.2019.8519.2044.3842。Conclusion:1) The protein diagnostic casts can be the potential biomarkers for EC diagnosis, potential EC biomarkers can be screened out by using SELDI-TOF-MS technology.2) Protein finger prints were significantly different among Han, Uygur and Kazakh in Xinjiang.M/Z 4310.0109 was low-expressed in Han EC patients and high-expressed in Uygur and Kazakh EC patients.But there was no differect between Uygur EC patients and Kazakh subjects. The established taxonomic tree model of Han, Uygur and Kazakh EC patients has high correct ration, specificity and sensitiveness. Therefore, to establish the EC diagnostic model of Han, Uygur and Kazakh EC patients in Xinjiang has a lot of clincal significance.3) M/Zs were significantly different between Kazakh EC patients of lymph node postive group, negative group and controls (P<0.05), which is 16081.0634,16152.0842,15962.2598,2019.8519,2044.3842。...