Department of General Surgery, Anhui Provincial Hospital Affiliated with Anhui Medical University, 17 Lujiang Road, Hefei 230001, Anhui Province, People's Republic of China.
J Cancer Res Clin Oncol. 2013 Jul;139(7):1117-27. doi: 10.1007/s00432-013-1422-4. Epub 2013 Apr 2.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide and is difficult to detect at its early stages when treatment is most effective. Therefore, we performed a comparative proteomic study to identify new biomarkers for the detection of PDAC.
Serum samples from patients with PDAC, chronic pancreatitis and normal controls were compared using two-dimensional difference gel electrophoresis (2D-DIGE). Differentially expressed separated proteins were subsequently identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Then, transthyretin (TTR), one of the differentially expressed proteins, was validated through real-time PCR, western blot and immunohistochemistry. Finally, enzyme-linked immunosorbent assays (ELISA) were employed to confirm the levels of transthyretin in the sera.
A total of 21 protein spots showed greater than 1.5-fold changes in expression level in the sera from PDAC patients compared with the normal controls. Among the identified proteins, validation experiments verified the differential expression of transthyretin in PDAC tissue, confirming the proteomic data showing that transthyretin was significantly elevated in patients with PDAC. The ELISA results revealed that the sensitivity and specificity for TTR and CA19-9 in distinguishing PDAC patients from normal individuals were 90.5, 47.6, 66.7 and 85.7 %, respectively, and 81.0 and 85.7 % for their combination.
These results suggest that the level of transthyretin is elevated in patients with PDAC. In combination with CA19-9, transthyretin may provide additional information for the detection of PDAC and should be further investigated.
胰腺导管腺癌（PDAC）是全球最致命的癌症之一，在治疗最有效的早期阶段很难发现。因此，我们进行了一项比较蛋白质组学研究，以确定用于检测 PDAC 的新生物标志物。
使用二维差异凝胶电泳（2D-DIGE）比较 PDAC 患者、慢性胰腺炎患者和正常对照者的血清样本。随后通过基质辅助激光解吸电离飞行时间质谱（MALDI-TOF/TOF-MS）鉴定差异表达的分离蛋白。然后，通过实时 PCR、western blot 和免疫组织化学验证差异表达蛋白之一转甲状腺素（TTR）。最后，通过酶联免疫吸附测定（ELISA）证实血清中转甲状腺素的水平。
与正常对照组相比，PDAC 患者血清中共有 21 个蛋白点的表达水平变化超过 1.5 倍。在鉴定出的蛋白中，验证实验证实了 TTR 在 PDAC 组织中的差异表达，证实了蛋白质组学数据表明 TTR 在 PDAC 患者中显著升高。ELISA 结果显示，TTR 和 CA19-9 用于区分 PDAC 患者与正常人的敏感性和特异性分别为 90.5%、47.6%、66.7%和 85.7%，联合使用时分别为 81.0%和 85.7%。
这些结果表明 TTR 在 PDAC 患者中升高。与 CA19-9 联合使用时，TTR 可能为 PDAC 的检测提供额外信息，应进一步研究。
