Department of Surgery, Institute of Molecular Medicine, Trinity Centre for Health Science, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
Ann Surg. 2011 Nov;254(5):809-16; discussion 816-7. doi: 10.1097/SLA.0b013e31823699f2.
To identify serum-based biomarkers predicting response to neoadjuvant chemoradiotherapy (neo-CRT) in esophageal cancer.
Increasingly, the standard of care for esophageal cancer involves neo-CRT followed by surgery. The identification of biomarkers predicting response to therapy may represent a major advance, enabling clinical trials and improved outcomes.
Patients with esophageal cancer (n = 31) received a standard neo-CRT regimen. Histopathologic response to therapy was assessed by using the Mandard tumor regression grade (TRG) classification. Serum was collected pretreatment and at 24-hour and 48-hour time points into treatment. Serum samples were analyzed by using Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and enzyme-linked immunosorbent assay. A leave-one-out cross-validation predictive algorithm assessed the ability of validated biomarkers to correctly predict therapeutic outcome.
Fifty-one percent (16) of patients were poor responders (TRG 3-5), whereas 49% (15) responded well (TRG 1-2). On CM10 biochips, serum expression of 9 protein peaks was significantly different between the response groups. Two differential spectrum peaks were identified as complement C4a and C3a and were subsequently analyzed by enzyme-linked immunosorbent assay. Pretreatment serum C4a and C3a levels were significantly higher in poor responders versus good responders. Subdivision of the response groups by TRG indicated an inverse correlation between levels of C4a and C3a and pathological response to neo-CRT. The leave-one-out cross-validation analysis revealed that these serum proteins could predict response to neo-CRT with a sensitivity and specificity of 78.6% and 83.3%, respectively.
This translational application of proteomics technology identifies pretreatment serum levels of C4a and C3a as predictive biomarkers of response. Large validation studies in an independent cohort are merited.
鉴定预测食管癌新辅助放化疗（neo-CRT）反应的血清生物标志物。
食管癌的标准治疗方法越来越多地涉及 neo-CRT 后再进行手术。鉴定预测治疗反应的生物标志物可能是一个重大进展，能够进行临床试验并改善结果。
31 例食管癌患者接受了标准 neo-CRT 方案。采用 Mandard 肿瘤消退分级（TRG）分类评估治疗的组织病理学反应。在治疗前、24 小时和 48 小时采集血清，并进行分析。使用表面增强激光解吸电离飞行时间质谱和酶联免疫吸附试验分析血清样本。采用留一法交叉验证预测算法评估经验证的生物标志物正确预测治疗结果的能力。
51%（16 例）的患者是不良反应者（TRG 3-5），而 49%（15 例）反应良好（TRG 1-2）。在 CM10 生物芯片上，反应组之间的 9 个蛋白质峰的血清表达差异显著。鉴定出两个差异光谱峰为补体 C4a 和 C3a，并随后通过酶联免疫吸附试验进行分析。不良反应者的预处理血清 C4a 和 C3a 水平明显高于良好反应者。按 TRG 对反应组进行细分表明，C4a 和 C3a 的水平与 neo-CRT 的病理反应呈反比关系。留一法交叉验证分析表明，这些血清蛋白对 neo-CRT 的反应具有 78.6%的灵敏度和 83.3%的特异性。
这项蛋白质组学技术的转化应用鉴定出预处理血清 C4a 和 C3a 水平可作为反应预测的生物标志物。值得在独立队列中进行大型验证研究。
