Validation Study of a Quantitative Multigene Reverse Transcriptase-Polymerase Chain Reaction Assay for Assessment of Recurrence Risk in Patients With Stage II Colon Cancer
Validation Study of a Quantitative Multigene Reverse Transcriptase-Polymerase Chain Reaction Assay for Assessment of Recurrence Risk in Patients With Stage II Colon Cancer
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DOI：
10.1200/jco.2010.32.8732
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发表时间：
2011-12-10
影响因子：
45.3
通讯作者：
Kerr, David J.
中科院分区：
文献类型：
--
作者：
Gray, Richard G.;Quirke, Philip;Kerr, David J.
目的我们开发了定量基因表达分析来评估II期结肠癌患者的复发风险和化疗的益处。患者和方法我们寻求通过从1436例II期结肠癌患者的固定石蜡包埋的原发结肠癌块中提取的RNA来验证在类星体(快速、简单和可靠)的辅助性氟嘧啶化疗和单纯手术研究中的有效性。根据13个癌相关基因(n=7个复发基因和n=6个治疗受益基因)和5个参考基因的基因表达水平，通过预先指定的算法计算复发评分(RS)和治疗评分(TS)。采用COX比例风险回归模型和LOG-RANK方法分析单纯手术患者的RS与复发风险之间的关系，以及TS与化疗益处之间的关系。结果复发风险与RS显著相关(每四分位数范围的危险比[HR]为1.38；95%CI为1.11~1.74；P=.004)。在预先确定的低、中、高复发风险组中，3年的复发风险分别为12%、18%和22%。T分期(HR，1.94；P<；.001)和错配修复(MMR)状态(HR，0.31；P<；.001)是最强的组织病理学预后因素。超过这些和其他协变量，连续RS与复发风险相关(P=.006)。结论连续12基因RS在一项前瞻性研究中已被用于评估II期结肠癌患者术后复发风险，并提供了补充T分期和MMR的预后价值。TS不能预测化疗的益处。
PurposeWe developed quantitative gene expression assays to assess recurrence risk and benefits from chemotherapy in patients with stage II colon cancer.Patients and MethodsWe sought validation by using RNA extracted from fixed paraffin-embedded primary colon tumor blocks from 1,436 patients with stage II colon cancer in the QUASAR (Quick and Simple and Reliable) study of adjuvant fluoropyrimidine chemotherapy versus surgery alone. A recurrence score (RS) and a treatment score (TS) were calculated from gene expression levels of 13 cancer-related genes (n = 7 recurrence genes and n = 6 treatment benefit genes) and from five reference genes with prespecified algorithms. Cox proportional hazards regression models and log-rank methods were used to analyze the relationship between the RS and risk of recurrence in patients treated with surgery alone and between TS and benefits of chemotherapy.ResultsRisk of recurrence was significantly associated with RS (hazard ratio [HR] per interquartile range, 1.38; 95% CI, 1.11 to 1.74; P = .004). Recurrence risks at 3 years were 12%, 18%, and 22% for predefined low, intermediate, and high recurrence risk groups, respectively. T stage (HR, 1.94; P < .001) and mismatch repair (MMR) status (HR, 0.31; P < .001) were the strongest histopathologic prognostic factors. The continuous RS was associated with risk of recurrence (P = .006) beyond these and other covariates. There was no trend for increased benefit from chemotherapy at higher TS (P = .95).ConclusionThe continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.