Surgery Branch, Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy.
Ann Surg Oncol. 2012 Feb;19(2):402-8. doi: 10.1245/s10434-011-2132-2. Epub 2011 Nov 10.
Although surgery is the gold standard treatment of hepatic metastasis from colorectal cancer (CRC), many patients ultimately die of their disease. We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurrence after apparently radical liver surgery.
We considered 50 patients undergoing radical surgery for liver-confined hepatic metastasis from CRC. The expression of a panel of cancer-related genes, as assessed by quantitative real-time PCR, was used to detect CTC in the peripheral blood of these patients immediately before surgery. Survival analysis was performed by the Cox regression model.
Univariate analysis of the expression levels of CD133 (a marker of colon cancer stem cells) and survivin (an antiapoptotic factor) resulted in statistically significant association with patient survival [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.9-3.7, P < 0.0001; and hazard ratio 2.1, 95% CI 1.4-3.2, P < 0.0001, respectively]. Remarkably, multivariate analysis found that only the transcriptional amount of CD133 resulted in statistical significance (HR 2.6, 95% CI 1.9-3.6, P < 0.0001), indicating that this biomarker can independently predict the survival of these patients.
CD133-positive CTC may represent a suitable prognostic marker to stratify the risk of patients who undergo liver resection for CRC metastasis, which opens the avenue to identifying and potentially monitoring the patients who are most likely to benefit from adjuvant treatments.
尽管手术是结直肠癌(CRC)肝转移的金标准治疗方法,但许多患者最终仍死于疾病。我们检验了这样一个假设,即循环肿瘤细胞(CTC)的检测可能会识别出在接受明显根治性肝手术后因疾病复发而死亡风险高的患者。
我们考虑了 50 名接受根治性手术治疗肝局限性结直肠癌肝转移的患者。通过定量实时 PCR 评估,用一组与癌症相关的基因表达谱来检测这些患者手术前外周血中的 CTC。采用 Cox 回归模型进行生存分析。
CD133(结肠癌细胞干细胞标志物)和生存素(抗凋亡因子)表达水平的单因素分析与患者生存呈统计学显著相关[风险比(HR)2.7,95%置信区间(CI)1.9-3.7,P<0.0001;和风险比 2.1,95%CI 1.4-3.2,P<0.0001]。值得注意的是,多因素分析发现只有 CD133 的转录量具有统计学意义(HR 2.6,95%CI 1.9-3.6,P<0.0001),表明该生物标志物可独立预测这些患者的生存情况。
CD133 阳性 CTC 可能是一种合适的预后标志物,可对接受 CRC 转移肝切除术的患者进行风险分层,这为识别和潜在监测最有可能从辅助治疗中获益的患者开辟了道路。