使用靶向二代测序检测子宫内膜癌、结肠癌和胃癌中的微卫星不稳定性
Detecting Microsatellite Instability in Endometrial, Colon, and Stomach Cancers Using Targeted NGS.
作者信息
Boyarskikh Ulyana, Kechin Andrey, Khrapov Evgeniy, Fedyanin Mikhail, Raskin Grigory, Mukhina Marina, Kravtsova Elena, Tsukanov Aleksey, Achkasov Sergey, Filipenko Maksim
机构信息
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
State Budgetary Institution of Health Care of Moscow (Moscow Multidisciplinary Clinical Center "Kommunarka"), 142770 Moscow, Russia.
出版信息
Cancers (Basel). 2023 Oct 20;15(20):5065. doi: 10.3390/cancers15205065.
PURPOSE
To develop a method for testing the MSI based on targeted NGS.
METHODS
Based on the results of previous studies, 81 microsatellite loci with high variability in MSI-H tumors were selected, and a method for calculating the MSI score was developed. Using the MSI score, we defined the MSI status in endometral (162), colon (153), and stomach (190) cancers. Accuracy of the MSI scores was evaluated by comparison with MMR immunohistochemistry for 137 endometrium (63 dMMR and 74 pMMR), 76 colon (29 dMMR and 47 pMMR), and 81 stomach (8 dMMR and 73 pMMR) cancers.
RESULTS
Classification of MSS and MSI-H tumors was performed with AUC (0.99), sensitivity (92%), and specificity (98%) for all tumors without division into types. The accuracy of MSI testing in endometrial cancer was lower than for stomach and colon cancer (0.98, 87%, and 100%, respectively). The use of 27 loci only, the most informative for endometrial cancer, increased the overall accuracy (1.00, 99%, and 99%). Comparison of MSI score values in 505 tumors showed that MSI score is significantly higher in colon ( < 10) and stomach ( = 0.008) cancer compared with endometrial cancer.
CONCLUSION
The MSI score accurately determines MSI status for endometrial, colon, and stomach cancers and can be used to quantify the degree of MSI.
目的
开发一种基于靶向二代测序（NGS）检测微卫星高度不稳定（MSI）的方法。
方法
基于既往研究结果，选择81个在MSI-H肿瘤中具有高变异性的微卫星位点，并开发一种计算MSI评分的方法。利用该MSI评分，我们定义了子宫内膜癌（162例）、结肠癌（153例）和胃癌（190例）的MSI状态。通过与137例子宫内膜癌（63例错配修复缺陷[dMMR]和74例错配修复正常[pMMR]）、76例结肠癌（29例dMMR和47例pMMR）以及81例胃癌（8例dMMR和73例pMMR）的错配修复蛋白免疫组化结果相比较，评估MSI评分的准确性。
结果
对所有肿瘤不分类型进行MSS和MSI-H肿瘤分类时，曲线下面积（AUC）为0.99，敏感性为92%，特异性为98%。子宫内膜癌MSI检测的准确性低于胃癌和结肠癌（分别为0.98、87%和100%）。仅使用对子宫内膜癌最具信息量的27个位点，可提高总体准确性（分别为1.00、99%和99%）。505例肿瘤的MSI评分值比较显示，与子宫内膜癌相比，结肠癌（<10）和胃癌（=0.008）的MSI评分显著更高。
结论
MSI评分可准确确定子宫内膜癌、结肠癌和胃癌的MSI状态，并可用于量化MSI程度。
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