Qi T, Han J, Cui Y, Zong M, Liu X, Zhu B
Key Laboratory of Ministry of Health for Biotech-Drug, Shandong Medicinal Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
J Clin Pathol. 2008 Jan;61(1):49-58. doi: 10.1136/jcp.2006.044735. Epub 2007 Apr 5.
To search for novel potential protein biomarkers for the early detection and better intervention of pancreatic ductal adenocarcinoma (PDAC).
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.
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.
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.
寻找用于胰腺导管腺癌（PDAC）早期检测及更好干预的新型潜在蛋白质生物标志物。
采用二维电泳对8对匹配的PDAC组织和非癌胰腺组织进行分析；通过质谱鉴定差异表达的蛋白质。利用组织芯片，采用免疫组织化学方法研究TBX4（T盒转录因子TBX4）和HSP60（60 kDa热休克蛋白）的表达模式。
共鉴定出48种差异表达的蛋白质；其中30种为新型潜在生物标志物。免疫组织化学显示，TBX4表达可见于正常胰腺的中央腺泡细胞和小导管以及5/5（100%）高分化、35/38（92.1%）中分化和11/18（61.1%）低分化PDAC组织的肿瘤细胞，染色强度不同。然而，在另外3/38（7.9%）中分化和7/18（38.9%）低分化PDAC组织的正常腺泡细胞和肿瘤细胞中，未见明显的TBX4表达。中分化和低分化PDAC组织中TBX4的表达差异具有统计学意义（p<0.01）。此外，TBX4阴性染色和阳性染色的肿瘤细胞在形态上存在明显差异，提示细胞起源不同。正常胰腺组织的腺泡细胞和小导管以及PDAC组织的肿瘤细胞（胰岛和肿瘤基质除外）中可见HSP60的强表达；未发现HSP60表达与PDAC组织分化之间存在相关性。
鉴定出30种在PDAC组织中差异表达的新型潜在生物标志物。TBX4可能是一种与分化相关的蛋白质；其对PDAC的预后价值值得进一步研究。
