Proteins with Altered Levels in Plasma from Glioblastoma Patients as Revealed by iTRAQ-Based Quantitative Proteomic Analysis

被引:68
作者
Gautam, Poonam [2 ]
Nair, Sudha C. [2 ]
Gupta, Manoj Kumar [2 ]
Sharma, Rakesh [1 ]
Polisetty, Ravindra Varma [2 ]
Uppin, Megha S. [3 ]
Sundaram, Challa [3 ]
Puligopu, Aneel K. [3 ]
Ankathi, Praveen [3 ]
Purohit, Aniruddh K. [3 ]
Chandak, Giriraj R. [2 ]
Harsha, H. C. [1 ]
Sirdeshmukh, Ravi [1 ,2 ]
机构
[1] Inst Bioinformat, Bangalore, Karnataka, India
[2] Ctr Cellular & Mol Biol CSIR, Hyderabad, Andhra Pradesh, India
[3] Nizams Inst Med Sci, Hyderabad, Andhra Pradesh, India
来源
PLOS ONE | 2012年 / 7卷 / 09期
关键词
CENTRAL-NERVOUS-SYSTEM; SERUM CARNOSINASE; CHROMOGRANIN-A; EXPRESSION; BRAIN; FERRITIN; MARKERS; CELLS; DIFFERENTIATION; INFLAMMATION;
D O I
10.1371/journal.pone.0046153
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Glioblastomas (GBMs) are the most common and lethal primary tumors of the central nervous system with high level of recurrence despite aggressive therapy. Tumor-associated proteins/peptides may appear in the plasma of these patients as a result of disruption of the blood-brain barrier in them, raising the scope for development of plasma-based tests for diagnosis and monitoring the disease. With this objective, we analyzed the levels of proteins present in the plasma from GBM patients using an iTRAQ based LC-MS/MS approach. Analysis with pooled plasma specimens from the patient and healthy control samples revealed high confidence identification of 296 proteins, of which 61 exhibited a fold-change >= 1.5 in the patient group. Forty-eight of them contained signal sequence. A majority have been reported in the differentially expressed transcript or protein profile of GBM tissues; 6 have been previously studied as plasma biomarkers for GBM and 16 for other types of cancers. Altered levels of three representative proteins-ferritin light chain (FTL), S100A9, and carnosinase 1 (CNDP1)-were verified by ELISA in a test set of ten individual plasma specimens. FTL is an inflammation marker also implicated in cancer, S100A9 is an important member of the Ca2+ signaling cascade reported to be altered in GBM tissue, and CNDP1 has been reported for its role in the regulation of the levels of carnosine, implicated as a potential drug for GBM. These and other proteins in the dataset may form useful starting points for further clinical investigations for the development of plasma-based biomarker panels for GBM.
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页数:11
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