Qiu Fu-Ming, Yu Jie-Kai, Chen Yi-Ding, Jin Qi-Feng, Sui Mei-Hua, Huang Jian
Department of Oncology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
J Exp Clin Cancer Res. 2009 Sep 9;28(1):126. doi: 10.1186/1756-9966-28-126.
Although gastric cancer (GC) remains the second cause of cancer-related death, useful biomarkers for prognosis are still unavailable. We present here the attempt of mining novel biomarkers for GC prognosis by using serum proteomics.
Sera from 43 GC patients and 41 controls with gastritis as Group 1 and 11 GC patients as Group 2 was successively detected by Surface Enhanced Laser Desorption/ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS) with Q10 chip. Peaks were acquired by Ciphergen ProteinChip Software 3.2.0 and analyzed by Zhejiang University-ProteinChip Data Analysis System (ZJU-PDAS). CEA level were evaluated by chemiluminescence immunoassay.
After median follow-up periods of 33 months, Group 1 with 4 GC patients lost was divided into 20 good-prognosis GC patients (overall survival more than 24 months) and 19 poor-prognosis GC patients (no more than 24 months). The established prognosis pattern consisted of 5 novel prognosis biomarkers with 84.2% sensitivity and 85.0% specificity, which were significantly higher than those of carcinoembryonic antigen (CEA) and TNM stage. We also tested prognosis pattern blindly in Group 2 with 66.7% sensitivity and 80.0% specificity. Moreover, we found that 4474-Da peak elevated significantly in GC and was associated with advanced stage (III+IV) and short survival (p < 0.03).
We have identified a number of novel biomarkers for prognosis prediction of GC by using SELDI-TOF-MS combined with sophisticated bioinformatics. Particularly, elevated expression of 4474-Da peak showed very promising to be developed into a novel biomarker associated with biologically aggressive features of GC.
尽管胃癌(GC)仍是癌症相关死亡的第二大原因,但仍缺乏有用的预后生物标志物。我们在此展示了通过血清蛋白质组学挖掘胃癌预后新生物标志物的尝试。
采用Q10芯片,通过表面增强激光解吸/电离飞行时间质谱(SELDI-TOF-MS)依次检测43例胃癌患者和41例胃炎对照患者(作为第1组)以及11例胃癌患者(作为第2组)的血清。通过Ciphergen ProteinChip Software 3.2.0获取峰,并由浙江大学蛋白质芯片数据分析系统(ZJU-PDAS)进行分析。通过化学发光免疫测定评估癌胚抗原(CEA)水平。
在中位随访33个月后,第1组中4例失访的胃癌患者被分为20例预后良好的胃癌患者(总生存期超过24个月)和19例预后不良的胃癌患者(不超过24个月)。所建立的预后模式由5种新的预后生物标志物组成,敏感性为84.2%,特异性为85.0%,显著高于癌胚抗原(CEA)和TNM分期。我们还在第2组中对预后模式进行了盲测,敏感性为66.7%,特异性为80.0%。此外,我们发现4474 - Da峰在胃癌中显著升高,且与晚期(III + IV期)和短生存期相关(p < 0.03)。
我们通过SELDI-TOF-MS结合精密的生物信息学鉴定了多种用于胃癌预后预测的新生物标志物。特别是,4474 - Da峰的表达升高显示出非常有希望被开发成为一种与胃癌生物学侵袭性特征相关的新生物标志物。