Department of Gastrointestinal Surgery, University of Sydney, Kolling Institute of Medical Research, St Leonards NSW 2065, Australia.
Br J Cancer. 2012 Nov 20;107(11):1883-91. doi: 10.1038/bjc.2012.458.
Pancreaticoduodenectomy remains a major undertaking. A preoperative blood test, which could confidently predict the benefits of surgery would improve the selection of pancreatic cancer patients for surgery. This study aimed to identify protein biomarkers prognostic for long-term survival and to validate them with clinico-pathological information.
Serum from 40 preoperative patients was used to train for predictive biomarkers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI), and the results were verified on 21 independent samples. Two predictive proteins were identified by tryptic peptide mass fingerprinting and sequencing, and validated on serum from another 57 patients by enzyme-linked immunosorbent assay (ELISA). The influence of these proteins on growth and invasion of two cancer cell lines was tested in-vitro.
The SELDI panel of m/z 3700, 8222 and 11 522 peaks predicted <12 months' survival (ROC AUC: 0.79, 0.64-0.90; P<0.039). When CA19-9 was added, the ROC AUC increased to 0.95 (0.84-0.99; P<0.0001). The six subjects in the verification group who died within 12 months were correctly classified. The m/z 8222 and 11 522 proteins were identified as Serum ApoC-II and SAA-1, respectively. In the validation samples, ELISA results confirmed that ApoC-II was predictive of survival (Kaplan-Meier P<0.009), but not SAA-I. ApoC-II, CA19-9 and major-vessel involvement independently predicted survival. ApoC-II and SAA-1 increased cell growth and invasion of both cancer cell lines.
Serum ApoC-II, CA19-9 and major-vessel invasion independently predict survival and improves selection of patients for pancreaticoduodenectomy.
胰十二指肠切除术仍然是一项重大的手术。如果有一种术前血液检测方法能够有信心地预测手术的获益，将有助于为胰腺癌患者选择手术。本研究旨在确定与长期生存相关的蛋白生物标志物，并通过临床病理信息进行验证。
使用表面增强激光解吸/电离飞行时间质谱（SELDI）对 40 例术前患者的血清进行预测生物标志物的训练，然后在 21 个独立样本中验证结果。通过胰酶肽质量指纹图谱和测序鉴定出两个预测蛋白，并用酶联免疫吸附试验（ELISA）在另外 57 例患者的血清中进行验证。在体外测试这些蛋白对两种癌细胞系生长和侵袭的影响。
SELDI 质谱 m/z 3700、8222 和 11522 峰的图谱预测 12 个月内生存<12 个月（ROC AUC：0.79、0.64-0.90；P<0.039）。当加入 CA19-9 时，ROC AUC 增加到 0.95（0.84-0.99；P<0.0001）。验证组中 6 例在 12 个月内死亡的患者得到了正确分类。m/z 8222 和 11522 蛋白分别被鉴定为血清载脂蛋白 C-II 和 SAA-1。在验证样本中，ELISA 结果证实 ApoC-II 与生存相关（Kaplan-Meier P<0.009），但 SAA-I 不相关。ApoC-II、CA19-9 和主要血管受累独立预测生存。ApoC-II 和 SAA-1 增加了两种癌细胞系的生长和侵袭。
血清 ApoC-II、CA19-9 和主要血管受累独立预测生存，并有助于为胰十二指肠切除术选择患者。
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