Brabender Jan, Vallböhmer Daniel, Grimminger Peter, Hoffmann Andreas C, Ling Frederike, Lurje Georg, Bollschweiler Elfriede, Schneider Paul M, Hölscher Arnulf H, Metzger Ralf
Department of Visceral and Vascular Surgery, University of Cologne, Joseph-Stelzmann Str. 9, 50931, Cologne, Germany.
J Gastrointest Surg. 2008 Nov;12(11):1815-21. doi: 10.1007/s11605-008-0668-7. Epub 2008 Sep 3.
The aim of this study was to determine the gene is spelled excision repair cross-complementing gene 1 (ERCC1) RNA-expression in peripheral blood as a non-invasive molecular predictor of response to neoadjuvant radio-chemotherapy in patients with locally advanced cancer of the esophagus.
Only patients with locally advanced cancer of the esophagus with a major histopathological response to neoadjuvant radio-chemotherapy benefit from this treatment. No non-invasive molecular marker exists that can reliably predict response to neoadjuvant therapy in this disease. To improve the treatment of patients with cancer of the esophagus, molecular predictors of response are desperately needed.
Blood samples were drawn from 29 patients with esophageal cancer prior to neoadjuvant radio-chemotherapy. After extraction of cellular tumor-RNA from blood samples, quantitative expression analysis of ERCC1 was done by real-time reverse transcription polymerase chain reaction.
Nineteen (65.5%) patients showed a minor and ten (34.5%) a major histopathological response to neoadjuvant therapy. ERCC1 expression in blood of patients was detectable in 82.8%. The median ERCC1 expression was 0.62 (minimum 0.00, maximum 2.48) in minor responders and 0.24 (minimum 0.00, maximum 0.45) in major responders (p = 0.004). No significant associations were detectable between ERCC1 levels and patients' clinical variables. Relative ERCC1 levels above 0.452 were not associated with major histopathological response (sensitivity, 68.4; specificity, 100%), and 13 of 19 patients with minor response could be unequivocally identified.
Minor responders to the applied therapy show a significant higher ERCC1 expression level in their blood compared to major responders. ERCC1 appears to be a highly specific non-invasive predictor of response to neoadjuvant therapy in esophageal cancer.
本研究旨在确定外周血中基因拼写为切除修复交叉互补基因1（ERCC1）的RNA表达情况，以此作为局部晚期食管癌患者新辅助放化疗反应的非侵入性分子预测指标。
仅对新辅助放化疗有主要组织病理学反应的局部晚期食管癌患者能从该治疗中获益。目前尚无可靠的非侵入性分子标志物可预测该疾病对新辅助治疗的反应。为改善食管癌患者的治疗，急需反应的分子预测指标。
在新辅助放化疗前，从29例食管癌患者中采集血样。从血样中提取细胞肿瘤RNA后，通过实时逆转录聚合酶链反应对ERCC1进行定量表达分析。
19例（65.5%）患者对新辅助治疗表现为轻微组织病理学反应，10例（34.5%）表现为主要组织病理学反应。82.8%的患者血液中可检测到ERCC1表达。轻微反应者的ERCC1表达中位数为0.62（最小值0.00，最大值2.48），主要反应者为0.24（最小值0.00，最大值0.45）（p = 0.004）。未检测到ERCC1水平与患者临床变量之间存在显著关联。ERCC1相对水平高于0.452与主要组织病理学反应无关（敏感性为68.4，特异性为100%），19例轻微反应患者中有13例可明确识别。
与主要反应者相比，接受治疗的轻微反应者血液中ERCC1表达水平显著更高。ERCC1似乎是食管癌新辅助治疗反应的高度特异性非侵入性预测指标。
