Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis.
OBJECTIVE
Sera from cancer patients contain tumor-specific autoantibodies directly against antigenic proteins. The identification of tumor autoantigens may have utility in cancer diagnosis, prognosis, and therapy. In this study, we used immunoproteomics analysis to identify tumor proteins that elicit humoral response in colorectal cancer (CRC).


METHODS
The CRC cell line HCT116 was used as a source of proteins for two-dimensional polyacrylamide gel electrophoresis and subsequent Western blot analysis in which individual serum from patients with CRC was analyzed for autoantibodies. Proteins that specifically react with sera from cancer patients were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis. In addition, the selected protein expression in tumor tissues collected from 40 patients with CRC were assessed by immunohistochemistry.


RESULTS
An autoantibody against inosine monophosphate dehydrogenase II (IMPDH2) identified by mass spectrometry was detected in eight out of 25 patients with CRC. However, none of the 15 healthy controls demonstrated autoantibody to IMPDH2.The expression of IMPDH2 in tumor tissue was significantly higher in patients with CRC than that in healthy subjects.


CONCLUSIONS
The result confirmed that the immunoproteomics analysis holds considerable promise for the discovery of tumor-associated antigens. IMPDH2 may be a protein biomarker and novel therapeutic target in CRC.
He
Yujun
Y
Department of General Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
Mou
Zhirong
Z
Li
Wanlin
W
Liu
Baohua
B
Fu
Tao
T
Zhao
Shong
S
Xiang
Debing
D
Wu
Yuzhang
Y
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D001323:Autoantibodies / Q000276:immunology; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007168:IMP Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D040901:Proteomics / Q000379:methods*; D012394:Rosaniline Dyes; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000951:Antigens, Neoplasm; D001323:Autoantibodies; D012394:Rosaniline Dyes; C048139:Coomassie blue; D007168:IMP Dehydrogenase; C501687:IMPDH2 protein, human