Comparative proteomic analysis for the detection of biomarkers in pancreatic ductal adenocarcinomas.
OBJECTIVE
To search for novel potential protein biomarkers for the early detection and better intervention of pancreatic ductal adenocarcinoma (PDAC).


METHODS
Eight pairs of matched PDAC and non-cancerous pancreas tissues were profiled with two-dimensional electrophoresis; differentially expressed proteins were identified by mass spectrometry. Expression patterns of TBX4 (T-box transcription factor TBX4) and HSP60 (60 KDa heat shock protein) were studied with immunohistochemistry using tissue microarrays.


RESULTS
A total of 48 differentially expressed proteins were identified; 30 of them are novel potential biomarkers. Immunohistochemistry showed that TBX4 expression could be seen in both centroacinar cells and small ducts in normal pancreas and tumour cells in 5/5 (100%) well differentiated, 35/38 (92.1%) moderately differentiated, and 11/18 (61.1%) poorly differentiated PDAC tissues with different staining intensity. However, in normal acinar cells and tumour cells in the other 3/38 (7.9%) moderately differentiated and 7/18 (38.9%) poorly differentiated PDAC tissues, there was no visible TBX4 expression. The expression difference of TBX4 between moderately differentiated and poorly differentiated PDAC tissues was statistically significant (p<0.01). In addition, there was obvious morphology difference between TBX4 negatively stained and positively stained tumour cells, which suggests different cellular origins. Strong expression of HSP60 could be seen in both acinar cells and small ducts in normal pancreas tissues and tumour cells in PDAC tissues except for islets and tumour stoma; no correlation was found between HSP60 expression and differentiation of PDAC tissues.


CONCLUSIONS
30 novel potential biomarkers differentially expressed in PDAC tissues were identified. TBX4 may be a differentiation related protein; its prognostic value for PDAC deserves further study.
Qi
T
T
Key Laboratory of Ministry of Health for Biotech-Drug, Shandong Medicinal Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
Han
J
J
Cui
Y
Y
Zong
M
M
Liu
X
X
Zhu
B
B
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics; D020825:T-Box Domain Proteins / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D014408:Biomarkers, Tumor; D050956:HSP40 Heat-Shock Proteins; D009363:Neoplasm Proteins; D020825:T-Box Domain Proteins; C491193:TBX4 protein, human; D014357:Trypsin