Advance Of Proteomics And Its Application In Gynecological Malignancy

With the completion of the human genome sequence project and the quick development of revelant techniques, proteomics is an emerging research area about the global protein profiles and their dynamic changes in cell. Technically, proteomics can be classified into two types. The first type is protein expression proteomics. It is the quantitative study of protein expressions between samples. The second type is functional proteomics. Analyzing protein profiles at subcellular sites is an important approach in understanding the functional organization of cells at the molecular level. The key techniques of proteomics are two-dimensional electrophoresis, mass spectrometry and bioinformatics. Proteomics has its origins in two-dimensional gel electrophoresis (2-DE) , a technique developed more than twenty years ago. 2-DE has a high resolution capacity, and was initially used primarily for separating and characterizing proteins in complex mixtures. The main objective of 2-DE is to obtain protein profiling. Using the two dimensional electrophoresis technique, the global proteins of tumor cells or tissues can be profiled first by their molecular weight and isoelectric point. After that, the specific interested protein can be indentified via mass spectrometry analysis combing with database searching. 2-DE has also been improved recently with the introduction of DIGE (differences gel electrophoresis) technology.This technology utilizes fluorescent tagging of two protein samples with two different dyes. These dyes are amine reactive and have the same molecular mass in order to eliminate mass differences between tagged samples. The tagged proteins are mixed together and run on the same 2-D gel. After image acquisition by a fluorescent scanner using different excitation wave length of each dye, the gel images are superimposed to identify differences. Another method for protein expression profiling has been invented, which does not require the separation of proteins by 2-DE. This method is called isotope-coded affinity tags (ICAT) . Protein samples from two different sources are labeled by two chemically identical reagents that differ only in mass as a result of isotope composition. Differential labeling of samples by mass allows the relative amount of proteins between two samples to be quantitated in the mass spectrometer. Proteins can usually be identified by using MS(mass spectrometry ) MALDI-MS (matrix-assisted laser desorption ionization mass spectrometer ) and SELDI-MS( surface enhanced laser desorption/ ionization mass spectrometry). Analogous to the DNA chip technologies, the Protein-Chip technology coupled with SELDI-TOF-MS (surface enhanced laser desorption / ionization time of flight mass spectrometry) has recently been developed. This technology utilizes patented Protein-Chip arrays to capture individual proteins from complex mixtures.By using the technology of proteomics, proteins expression amount, position and modified status could be compared between normal and tumor cells and tissues. Some tumor specific proteins can be found which may be involved in tumorogenesis. These proteins will be better markers diagnosis, evaluation of treatment and prognosis for tumors of gynecologic malignancy.Studying of proteomics in the ovarian cancer discovered .(1)Application of LCM, SELDI-TOF-MS and two-dimensional gel electrophoresi was advantaged of evaluating the pathogenesis.(2) In serum and ascites samples of ovarian cancers, FK506 binding protein Rho-G-protein dissociation inhibitors haptoglobin2a1 lysophosphatidyleth -anolamine ( LPA ) could be used as marker(s) of diagnosis and follow-up .(3) Findings demonstrated that enhanced protein expression such as PCAN, 18 (Op 18) ,calreticulin,HSP60 and HSP90 were advantage of treatment and prognosis of ovarian cancers.(4)By using laser capture microdissection and two-dimensional gelelectrophoresis,findings indicated that the high express of Rho G - protein dissociation inhibitor (RhoGDI) was closely correlated with the ovarian cancer cell apotosis and resistance.Studying of differentiate cervical cancer by the protein biochip SELDI approach found that seven proteins appeared to be down regulated in cervical cancer. It indicated that the proteomics approach of SELDI mass spectrometry, in combination with a simple scoring system might potentially be used in the early diagnosis of invasive cervical cancer. In addition, the identification of these specific proteins in cervical cancer may also facilitate the discovery of new cervical tumor marker(s).There were more factors that slowed developing of proteomics technicas, for example, the study of low-copy number proteins, but from the new point of view, proteomics may play a vital role in the early detection and prognosis of gynecologic malignancy by looking for tumor specific protein and elucidating the relationship between the change of expression and different phases of tumorogenesis.