Department of Surgery, Division of Surgical Oncology, Emory University, Atlanta, GA 10065, USA.
Surgery. 2012 Feb;151(2):162-70. doi: 10.1016/j.surg.2011.07.020. Epub 2011 Oct 6.
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.
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 thymidylate synthase (TS; 5-fluorouracil), excision repair cross complementing gene-1, 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.
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 < .0001] and 50% vs. 80% [P < .0001], respectively). Of the 12 genes studied, only increased TS expression was associated with a lower RFS (hazard ratio, 1.16; 95% confidence interval, 1.0-1.3; P = .03) and DSS (hazard ratio, 1.25; 95% confidence interval, 1.0-1.5; P = .03). Median RFS and 3-year DSS for patients with increased TS expression was decreased (9 vs. 15 months [P = .03] and 48% vs. 82% [P = .001], respectively). TS expression had prognostic value that was independent of CRS on multivariate analysis.
In patients with hepatic CRCLM treated with resection and modern chemotherapy, increased expression of TS improves outcome stratification and appears to be a useful biomarker.
在接受切除术和现代化疗治疗的结直肠癌肝转移（CRCLM）患者中，特定肿瘤基因表达变化的预后相关性尚不清楚。
研究了 2000 年 1 月至 2007 年 10 月期间接受肝切除术的 CRCLM 患者。为每位患者计算临床风险评分（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 个具有化疗耐药和肿瘤进展潜在重要性的基因的定量表达，包括胸苷酸合成酶（TS；5-氟尿嘧啶）、切除修复交叉互补基因-1 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 和肝细胞生长因子。主要结局是肝切除后无复发生存（RFS）和疾病特异性生存（DSS）。
确定了 155 例具有高质量肿瘤 mRNA 的患者。幸存者的中位随访时间为 32 个月，中位 CRS 为 2。87 例（56%）患者接受术前化疗，124 例（80%）患者接受术后化疗。所有患者的中位 RFS 为 13 个月，3 年 DSS 为 69%。CRS（3-5）升高的患者的中位 RFS 和 3 年 DSS 较低（7 个月对 18 个月[P<0.0001]和 50%对 80%[P<0.0001]）。在研究的 12 个基因中，只有 TS 表达增加与较低的 RFS（风险比，1.16；95%置信区间，1.0-1.3；P=0.03）和 DSS（风险比，1.25；95%置信区间，1.0-1.5；P=0.03）相关。TS 表达增加的患者中位 RFS 和 3 年 DSS 降低（9 个月对 15 个月[P=0.03]和 48%对 82%[P=0.001]）。在多变量分析中，TS 表达的预后价值独立于 CRS。
在接受切除术和现代化疗治疗的结直肠癌肝转移患者中，TS 表达增加可改善预后分层，似乎是一种有用的生物标志物。
