Dundee Cancer Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
Br J Cancer. 2012 Feb 28;106(5):955-61. doi: 10.1038/bjc.2012.15. Epub 2012 Jan 31.
The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer.
Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression).
Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival.
Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer.
食管腺癌的发病率在全球范围内呈上升趋势，但生存率仍然较低。新辅助化疗可以提高生存率，但需要预测和预后的生物标志物。本研究基于临床前方法，旨在确定食管癌的预后血浆蛋白质组学标志物。
通过表面增强激光解吸/电离飞行时间（SELDI-TOF）质谱（MS）分析收集的食管癌和非癌症对照患者治疗前后的血浆样本。通过 MS 在纯化部分的胰蛋白酶消化物中鉴定蛋白质峰。通过单变量（Fisher 精确检验）和多变量分析（二元逻辑回归）测试光谱中获得的峰强度与临床终点（生存、无病生存）之间的相关性。
在基线时，食管癌组和对照组之间的血浆蛋白峰差异有统计学意义（P<0.05，方差分析）。基线（治疗前）样本中三种被确认为载脂蛋白 A-I、血清淀粉样蛋白 A 和转甲状腺素的蛋白峰，通过单变量和多变量分析与无病生存和总生存相关。
可以在治疗食管癌之前检测到与预后相关的血浆蛋白，这些蛋白可作为预测和预后标志物，以指导食管癌化疗的反应。
