Improving the clinical risk score: An analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases
Improving the clinical risk score: An analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases
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DOI：
10.1016/j.surg.2011.07.020
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发表时间：
2012-02-01
期刊：
影响因子：
3.8
通讯作者：
D'Angelica, Michael I.
中科院分区：
文献类型：
--
作者：
Maithel, Shishir K.;Goenen, Mithat;D'Angelica, Michael I.
背景结直肠癌肝转移（CRCLMs）患者行切除术和现代化疗后，特异性肿瘤基因表达的变化与预后的相关性尚不清楚。研究对象为2000年1月至2007年10月期间因CRCLM接受肝切除术的患者。计算每例患者的临床风险评分（CRS;范围，0-5）。从组织学证实的肿瘤分离物中提取RNA，并使用实时聚合酶链反应（PCR）研究，我们评估了12个基因的定量表达，这些基因在化疗耐药性和肿瘤进展中具有潜在的重要性，包括胸苷酸合成酶（TS; 57氟尿嘧啶）、切除修复交叉互补基因-I和着色性干皮病组A至G（奥沙利铂），拓扑异构酶-I（伊立替康），c-met，.主要结果是肝切除术后的无复发生存率（RFS）和疾病特异性生存率（DSS）。鉴定了155名具有良好质量肿瘤mRNA的患者。存活者的中位随访时间为32个月，中位CRS为2。87例患者（56%）接受术前化疗，124例（80%）接受术后化疗。所有患者的中位RFS为13个月，3年DSS为69%。CRS增加（3-5）的患者的中位RFS和3年DSS较低（7 vs 18个月[P
Background. The prognostic relevance of variations in expression of specific tumor genes in colorectal cancer liver metastases (CRCLMs) in patients treated with resection and modern chemotherapy is not known.Methods. Patients submitted to liver resection for CRCLM between January 2000 and October 2007 were studied. A clinical risk score (CRS; range, 0-5) was calculated for each patient. RNA was extracted from histologically confirmed tumor isolates, and using real-time polymerase chain reaction (PCR) studies, we assessed the quantitative expression of 12 genes with potential importance in chemotherapy resistance and tumor progression, including thymidy late synthase (TS; 57fluorouracil), excision repair cross complementing gene-I, and xeroderma pigmentosum groups A through G (oxaliplatin), topoisomerase-I (irinotecan), c-met,. and hepatocyte growth factor Primary outcomes were recurrence-free survival (RFS) and disease-specific survival (DSS) after hepatic resection.Results. One-hundred fifty-five patients with good quality tumor mRNA were identified. Median follow-up was 32 months for survivors, and the median CRS was 2. Eighty-seven patients (56%) received preoperative chemotherapy, and 124 (80%) received postoperative chemotherapy. Median RFS for all patients was 13 months, and 3-year DSS was 69%. Median RFS and 3-year DSS for patients with an increased CRS (3-5) was lower (7 vs 18 months [P