Comparative Study Of Serum Proteomes In Patients With Hypothalamic Injury Follwing Excision Of Craniopharyngioma

Background and Objective:craniopharyngioma(CPs)that inner layer is covered by the stratified squamous epithelium,which arises from the residual embryonic cells of hypophyseal-pharyngeal duct,and found at the upper edge of the pituitary gland.However,some CPs can occur in the third ventricle,or the tumors originate from pituitary,pituitary stalk and hypothalamus.Considering anatomical position in the respective of hypothalamus,pituitary stalk,optic chiasma,and other important structures,CP treatment remains a huge challenge for neurosurgeons due to risky surgery and postoperative complications.So it always accompany hypothalamic injury following the resection of CPs,which causes severe side effects for the patients,including serum electrolyte disorder,obesity,hyperthermia or hypothermia.At present,the majority of scholars mainly based on animal experiments or clinical cases research.It is very rare about serum differential proteomic analysis after hypothalamic injury followed craniopharyngioma resection.In this study,the serum protein spectrum analysis was conducted by the iTRAQ marker and the differentially expressed proteins were screened out,then bioinformatics analysis was performed in the candidate biomarkers.Methods:The study included a total of 5 patients followed endoscopic endnasal craniopharyngioma resection at the first affiliated hospital of Nanchang University from june to december in 2017,serum samples were collected from the 5 patients and 5 matched healthy volunteers.The sample included 5 preoperative blood serum samples,5 blood serum samples for the first time sampled after operation,5 blood serum samples for the second times sampled after operation and 5 heathy control blood serum samples,then defined the samples as group A?group B?group C and goup D respectively.This study using the isobaric tags for relative and absolute quantification(iTRAQ)technique.Further compared LC-MS/MS results of each group of blood serum samples and evaluated the differential quantification of proteins.The prime datas of LC-MS/MS analysed by ProteomeDiscoverer system according to the filter parameter(FDR<0.01).The statistical significance of the differential expression levels on proteins was tested by t-test(P<0.05).Then the differentially expressed proteins were screened out for further bioinformation analysis,included Gene ontology analyses,KEGG pathway and PPI functional network analyses.Results:In this study,iTRAQ labeled LC-MS/MS protein profile of each serum sample was performed for qualitative and quantitative proteomic analysis.Totally,in this study 960 proteins were indentified in the serum samples.Among these,compared with the results of group A,110 proteins were significantly up-regulation among the group D,116 proteins were down-regulation.Compared with the results of group A,120 proteins were highly up-regulation in the group B,accompanied by the descending expressive of 90 proteins.Then compared with the results of group B,71 proteins were highly up-regulation in the group C,accompanied by the descending expressive of 71 proteins.Then the differential expressed proteins of each groups were proceed to GO and KEGG analysis,it reveals that the functions of these proteins are mainly Binding,Catalytic activity,Molecular function regulator,Structural molecular activity and Transporter activity.And these proteins are manly participate in biological process,such as Cellular process,Metabolic process,Response to stimulus and Regulation of biological process et al.A dynamic analysis of the proteins with distinct differences between the groups was carried out,combined with 5 cases' medical history and physical condition changes,the following candidate protein genes were screened out,the proteins of COL1A1?COL1A2?NUCB1?RPS18?CCDC81?ANGPTL8?LSAMP?Leptin?APOA4 ? CBLN2 ? CA1 et al maybe highly correspond with the change of hypothalamus after operation.Finally,the candidate marker proteins screened by bioinformatics analysis methods,and further understood their postion in pathway network and protein interaction tree,provide a supportive role for the further research study.Conclusions:The candidate marker proteins in the serum of craniopharyngioma patients were screened by iTRAQ labeled LC-MS/MS serum protein profile before and after surgical procedure and analyzed by bioinformatics GO and KEEG for the presence of candidate serum proteins in the pathway,then establish classification tree model.We concluded that the protein CA1 were significantly correlated to postoperative serum electrolyte imblance,the proteins Leptin and NUCB1 were significantly correlated to postoperative obesity and weight gain,and LSAMP were significantly correlated to emotional regulation or mental disorder of hypothalmus.This research study provide certain protein factors which may used for predicating the postoperative complications of craniopharyngioma,and also found certain new protein target for further treatment of the severity complications,such as serum electrolyte disorder,obesity control,hypothermia or hyperthermia,diabete insipidus et al.However,the most important is that our study also provide a strong supportive role in the next reseaches.