While the ICAT reagent only interacts with the free sulfhydryl of homocysteine and 8% protein is noncysteine, the SILAC has emerged as a valuable proteomic technique [98] which becomes more common for cell types and have been applied in many fields [99] [100] [101] . The SILAC technique can be effectively expanded to compare the differential expression levels of tissue proteome at different pathological states, which allows to identify new candidate biomarkers [102] . Compared with the ICAT, a popular in vitro labeling, SILAC as an example of in vivo coding requires no chemical manipulation, and there is very little chemical difference between the isotopically labeled amino acid and its naturally occurring counterpart [103] . In addition, the amount of labeled proteins requires for analysis using SILAC technique is far less than that with ICAT. Therefore, the SILAC-based method has broadly applied in many areas of cell biology and proteomics. Except that the SILAC-based quantitative method is powerful in comparative/differential proteomics, it has been widely used in analyzing protein posttranslational modification, such as protein phosphorylation, detection of protein-protein or peptide-protein interactions and investigating signal transduction pathways [104, 105] .Though there are numerous advantages for using SILAC-based methods compared to chemical labeling, a major drawback of SILAC is that it cannot be applied to tissue protein analysis directly. To overcome this shortcoming, SILAC has been successfully applied to tissue proteome based on 15 N isotope labeling [106] . Microorganisms such as malaria parasite can be labeled with isoleucine [107] . Latterly the culturederived isotope tags (CDITs) method was developed as an alternative quantitative approach for studying the proteome of mammalian tissues based on the application of SILAC [108] .