Predictive model for high-frequency microsatellite instability in colorectal cancer patients over 50 years of age.
Predictive model for high-frequency microsatellite instability in colorectal cancer patients over 50 years of age.
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DOI：
10.1002/cam4.1088
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发表时间：
2017-06
期刊：
影响因子：
4
通讯作者：
Akagi K
中科院分区：
文献类型：
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作者：
Fujiyoshi K;Yamaguchi T;Kakuta M;Takahashi A;Arai Y;Yamada M;Yamamoto G;Ohde S;Takao M;Horiguchi SI;Natsume S;Kazama S;Nishizawa Y;Nishimura Y;Akagi Y;Sakamoto H;Akagi K
微卫星不稳定性（MSI）是筛查Lynch综合征的重要生物标志物，也是对免疫检查点抑制剂的反应。本研究的目的是建立一个预测模型，以确定哪些老年结直肠癌（CRC）患者应该接受MSI和/或免疫组化检测的基础上，临床病理数据。我们通过多变量logistic回归分析分析了年龄≥50岁的CRC患者（n = 2219）的测试队列，以确定高频MSI（MSI-H）的预测因子。在外部队列（n = 992）中验证了创建的预测模型。在年龄≥ 50岁的CRC患者中，MSI‐H的频率为5.5%。在试验队列中确定了以下5个MSI-H预测因子：女性（1分）、粘液成分（2分）、肿瘤大小≥ 60 mm（2分）、近端结肠位置（3分）和BRAF突变（6分）。该预测模型的受试者工作特征（ROC）分析中的曲线下面积（AUC）为0.832（95%置信区间：0.790-0.874）。临界值为4分时，敏感性和特异性分别为74.4%和77.7%。验证队列的受试者工作特征曲线也显示AUC为0.856（95% CI：0.806-0.905）。该预测模型可用于选择应接受MSI检测的老年CRC患者，以及可能从基于5-FU的辅助化疗和癌症免疫治疗中获益的患者。
Microsatellite instability (MSI) is an important biomarker for screening for Lynch syndrome, and also of response to immune checkpoint inhibitors. The aim of this study is to create a predictive model to determine which elderly patients with colorectal cancer (CRC) should undergo MSI and/or immunohistochemistry testing on the basis of clinicopathological data. We analyzed a test cohort of CRC patients aged ≥50 years (n = 2219) by multivariate logistic regression analyses to identify predictors of high‐frequency MSI (MSI‐H). The created prediction model was validated in an external cohort (n = 992). The frequency of MSI‐H was 5.5% among CRC patients aged ≥ 50 years. The following five predictors of MSI‐H were identified in the test cohort: female (1 point), mucinous component (2 points), tumor size ≥ 60 mm (2 points), location in proximal colon (3 points), and BRAF mutation (6 points). The area under curve (AUC) in the receiver‐operating characteristic (ROC) analysis of this prediction model was 0.832 (95% confidence interval: 0.790–0.874). The sensitivity and specificity were 74.4% and 77.7%, respectively, for a cut‐off score of 4 points. The receiver‐operating characteristic curve of the validation cohort also showed an AUC of 0.856 (95% CI: 0.806–0.905). This prediction model is useful to select elderly CRC patients who should undergo MSI testing, and who may benefit from treatment with 5‐FU‐based adjuvant chemotherapy and cancer immunotherapy.