The Clinical Applied Research Of Protein Fingerprint Models In Glioma

Glioma is the most common malignant tumor among brain tumors, and ranked the tenth in cancer-related deaths in China and tenth in frequency in men and women. One of the most important factors caused high mortality rate is lacking effective means for the qualitative diagnosis at its preoperative stages, which can be helpful to take radiotherapy or other therapy on glioma patients before operation and to define resecting scope once performing operation. Furthermore, because pathological grading is very closing associated to prognosis, it's important to identify new prognostic factors. What is more, the recurrence of glioma is the puzzle for enhancing the prognosis of glioma at long- term, so how to monitor recurrence after operation is an urgent affair.Currently, it is very difficult in prognosis valuation and recurrence monitoring after operation. Although imagine technique has made great progress, the useful non-invasive detection techniques for clinical screening are lacking. The classification of glioma at pre-operation stage can very facilitative to estimate the malignant degree for surgeon. The WHO (2000) grading is commonly used for pathological classification postoperatively, so far, mere has no appropriate way to evaluate the malignant degree before operation. On the other hand, monitoring recurrence after operation can be worthy in improving long-term survival rate for glioma patients, so it is essential to develop more accurate and sophisticated methods to evaluate the malignant degree before operation and to monitor recurrence after operation.Because of the multifactorial nature of the glioma, it is very likely that a combination of several markers will be necessary to effectively detect and valuate prognosis of glioma. Proteomic methods detect the functioning units of expressed genes, through biochemical analysis of cellular proteins, to provide a protein fingerprint. The proteomic reflects both the intrinsic genetic programme of the cell and the impact of its immediate environment and is therefore valuable in biomarker discovery. Distinct changes that occur at the protein level during the transformation of a normal cell into a neoplastic cell include altered expression, differential protein modification, changes in specific activity, and inappropriate localization, all of which may affect cellular function. SELDI-TOF(surface-enhanced laser desorption/ionization time of flight) mass spectrometry is one of the recently developed sophisticated technologies, which, based on capturing proteins/peptides by chemically modified surface, is specifically powerful for analyzing the complex biological samples. This technology, combined with bioinformatics, has been successfully used to analyze the complex serum proteins to explore the cancer-specific 'fingerprints' or 'patterns'. Materials and MethodsSeventy-two cerebrospinal fluid samples, 105 serum samples (including 8 recurred cases) and 12 self-pairs brain tissues (glioma tissues and those self-pair tumor-side tissues, including 4 self-pair recurring cases) were detected by SELDI-TOF-MS. The data of spectra were analyzed by the bioinformatics tools like artificial neural network (ANN), support vector machine (SVM), discriminant analysis. Using SELDI-TOF-MS, we expect to find out new methods for qualitative diagnosis before operation, analyze some undocumented prognostic factors and create an individual risk assessment model for predicting the recurrence of the patients with glioma. Results1 Chip selectionThe protocol constitution of the serum protein profiling for glioma and the selection of protein chips: The modified protocol of serum protein profiling was stable and repeatable. After comparing four type protein chips of IMAC, WCX-2, CM 10, and H4, CM 10 used for serum biomarker discovery of the glioma have the advantage over other chips. CM 10 chip is attributed to WCX-2, is more stable than other chips (Its CV value is the least among the four chips), so we select it to detect serum spectrometric proteins. The protocol constitution of the cerebrospinal protein...