Relationship Between Tumor Gene Expression and Recurrence in Four Independent Studies of Patients With Stage II/III Colon Cancer Treated With Surgery Alone or Surgery Plus Adjuvant Fluorouracil Plus Leucovorin
Relationship Between Tumor Gene Expression and Recurrence in Four Independent Studies of Patients With Stage II/III Colon Cancer Treated With Surgery Alone or Surgery Plus Adjuvant Fluorouracil Plus Leucovorin
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DOI：
10.1200/jco.2010.28.9538
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发表时间：
2010-09-01
影响因子：
45.3
通讯作者：
Wolmark, Norman
中科院分区：
文献类型：
--
作者：
O'Connell, Michael J.;Lavery, Ian;Wolmark, Norman
目的这些研究旨在确定单纯手术或手术加氟尿嘧啶（FU）和甲酰四氢叶酸（LV）治疗的II或III期结肠癌患者中定量肿瘤基因表达与癌症复发风险之间的关系，以开发多基因算法来定量复发风险以及FU/LV治疗的差异治疗益处的可能性。患者和方法我们对从固定的，石蜡包埋（FPE）肿瘤块，来自仅接受手术治疗的II期或III期结肠癌患者（n = 270来自国家外科辅助乳腺和肠道项目[NSABP] C-01/C-02，n = 765来自克利夫兰诊所[CC]）或手术+FU/LV（n = 308来自NSABP C-04，n = 508来自NSABP C-06）。共研究了761个候选基因，CC/C-06共研究了375个基因。结果4项研究的联合分析确定了48个与复发风险显著相关的基因和66个与FU/LV获益显著相关的基因（其中4个基因相同）。七个复发风险基因，六个FU/LV受益基因，和五个参考基因被选中，并开发算法，以确定低，中，高复发和FU/LV受益的可能性的患者组。结论RT-qPCR的FPE结肠癌组织应用于四个大的独立人群已被用于开发多基因算法，估计复发风险和FU/LV受益。这些算法正在进行独立验证，其临床实用性正在快速、简单和可靠（QUASAR）研究中进行评估。
PurposeThese studies were conducted to determine the relationship between quantitative tumor gene expression and risk of cancer recurrence in patients with stage II or III colon cancer treated with surgery alone or surgery plus fluorouracil (FU) and leucovorin (LV) to develop multigene algorithms to quantify the risk of recurrence as well as the likelihood of differential treatment benefit of FU/LV adjuvant chemotherapy for individual patients.Patients and MethodsWe performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) on RNA extracted from fixed, paraffin-embedded (FPE) tumor blocks from patients with stage II or III colon cancer who were treated with surgery alone (n = 270 from National Surgical Adjuvant Breast and Bowel Project [NSABP] C-01/C-02 and n = 765 from Cleveland Clinic [CC]) or surgery plus FU/LV (n = 308 from NSABP C-04 and n = 508 from NSABP C-06). Overall, 761 candidate genes were studied in C-01/C-02 and C-04, and a subset of 375 genes was studied in CC/C-06.ResultsA combined analysis of the four studies identified 48 genes significantly associated with risk of recurrence and 66 genes significantly associated with FU/LV benefit (with four genes in common). Seven recurrence-risk genes, six FU/LV-benefit genes, and five reference genes were selected, and algorithms were developed to identify groups of patients with low, intermediate, and high likelihood of recurrence and benefit from FU/LV.ConclusionRT-qPCR of FPE colon cancer tissue applied to four large independent populations has been used to develop multigene algorithms for estimating recurrence risk and benefit from FU/LV. These algorithms are being independently validated, and their clinical utility is being evaluated in the Quick and Simple and Reliable (QUASAR) study.