IGFBP-3 Gene Methylation in Primary Tumor Predicts Recurrence of Stage II Colorectal Cancers.
IGFBP-3 Gene Methylation in Primary Tumor Predicts Recurrence of Stage II Colorectal Cancers.
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DOI：
10.1097/sla.0000000000001204
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发表时间：
2016-02
影响因子：
9
通讯作者：
Ahuja N
中科院分区：
文献类型：
--
作者：
Fu T;Pappou EP;Guzzetta AA;Calmon Mde F;Sun L;Herrera A;Li F;Wolfgang CL;Baylin SB;Iacobuzio-Donahue CA;Tong W;Ahuja N
评价IGFBP-3甲基化对2个独立队列II期结直肠癌（CRC）患者复发的影响。原发性肿瘤（PT）或淋巴结（LN）中IGFBP-3甲基化与仅接受手术治疗的II期CRC患者复发风险之间的关系尚不清楚。分析了来自2个独立队列的II期CRC患者中115个PT和1641个LN的IGFBP-3 DNA甲基化。40例患者复发，而75例匹配的患者在手术后2年以上无复发。使用考克斯比例风险模型计算复发风险比（HR），并根据患者和肿瘤特征进行校正。PT中IGFBP-3的甲基化被确定为与训练集中的复发风险显著相关。该签名在验证集中进行了测试，并将40.7%的患者归类为高风险。低风险和高风险患者的5年无复发生存率分别为76.4%和58.3%，HR为2.21（95%置信区间，1.04-4.68; P = 0.039）。在多变量分析中，签名仍然是最重要的预后因素，HR为2.40（95%置信区间，1.10-5.25; P = 0.029）。对来自2组的1641例LN的联合分析发现，LN中的IGFBP-3甲基化与复发风险无关。在PT中检测IGFBP-3甲基化，而不是在LN中，为识别具有高复发风险的II期CRC患者提供了一个强有力的工具。
To evaluate the influence of IGFBP-3 methylation on recurrence in patients with stage II colorectal cancer (CRC) from 2 independent cohorts. The relationship between IGFBP-3 methylation in primary tumors (PTs) or lymph nodes (LNs) and risk of recurrence in patients with stage II CRC treated with surgery alone is unknown. IGFBP-3 methylation of DNA from 115 PTs and 1641 LNs in patients with stage II CRC from 2 independent cohorts was analyzed. Forty patients developed recurrence, whereas 75 matched patients remained recurrence free for more than 2 years after surgery. Cox proportional hazard models were used to calculate hazard ratios (HRs) of recurrence, adjusted for patient and tumor characteristics. Methylation of IGFBP-3 in PTs was identified to be significantly associated with risk of recurrence in the training set. The signature was tested in a validation set and classified 40.7% of patients as high risk. Five-year recurrence-free survival rates were 76.4% and 58.3% for low- and high-risk patients, respectively, with an HR of 2.21 (95% confidence interval, 1.04–4.68; P = 0.039). In multivariate analysis, the signature remained the most significant prognostic factor, with an HR of 2.40 (95% confidence interval, 1.10–5.25; P = 0.029). A combined analysis of 1641 LNs from the 2 sets identified IGFBP-3 methylation in LNs was not associated with risk of recurrence. Detection of IGFBP-3 methylation in PTs, but not in LNs, provides a powerful tool for the identification of patients with stage II CRC at high risk of recurrence.