Department of Biology, Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran.
Department of Cancer, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Cell Physiol. 2019 Aug;234(8):13128-13136. doi: 10.1002/jcp.27983. Epub 2018 Dec 13.
Microsatellite instability (MSI) is a prognostic marker in colorectal cancer (CRC). The biological significance of MSI-low (MSI-L) phenotype and its differences with microsatellite stable (MSS) phenotype remains unclear. The aim of this study is indicating the role of mononucleotide repeat in identifying MSI-L and revealing the association of MSI-L with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) and oncologic outcome in CRC patients.
MSI and EMAST status were analyzed using three quasimonomorphic panel (BAT-25, BAT-26, and NR-27) and five tetranucleotide repeats (D20S82, D20S85, D9S242, D8S321, and MYCL1), respectively, by capillary electrophoresis method without the need to fluorescent primers. The associations of MSI status with clinicopathological features, EMAST status, metastasis, and overall survival (OS) were investigated.
Among 159 CRC patient 22.0% were MSI-H, 40.3% were MSS, 37.7% were MSI-L, and 41.5% showed EMAST + phenotype. MSI-L were associated with advanced stages, EMAST tumors and worse OS ( p ≤ 0.001). Metastasis was relatively common in MSI-L/EMAST CRCs and BAT-25 were the most unstable marker in these tumors.
MSI-L tumors have different clinicopathological features from MSS and MSI-H tumors. The MSI-L phenotype is a worse prognostic biomarker in CRC and when accompanied by EMAST could be a predictor for metastasis.
微卫星不稳定性（MSI）是结直肠癌（CRC）的一种预后标志物。MSI-低（MSI-L）表型的生物学意义及其与微卫星稳定（MSS）表型的差异尚不清楚。本研究旨在指出单核苷酸重复在识别 MSI-L 中的作用，并揭示 MSI-L 与 CRC 患者中选定的四核苷酸重复（EMAST）升高的微卫星改变和肿瘤学结果之间的关联。
使用毛细管电泳法，无需荧光引物，通过三个拟单相面板（BAT-25、BAT-26 和 NR-27）和五个四核苷酸重复（D20S82、D20S85、D9S242、D8S321 和 MYCL1）分别分析 MSI 和 EMAST 状态。研究了 MSI 状态与临床病理特征、EMAST 状态、转移和总生存期（OS）的关系。
在 159 例 CRC 患者中，22.0%为 MSI-H，40.3%为 MSS，37.7%为 MSI-L，41.5%为 EMAST+表型。MSI-L 与晚期分期、EMAST 肿瘤和更差的 OS 相关（p≤0.001）。MSI-L/EMAST CRC 中转移相对常见，并且这些肿瘤中 BAT-25 是最不稳定的标志物。
MSI-L 肿瘤与 MSS 和 MSI-H 肿瘤具有不同的临床病理特征。MSI-L 表型是 CRC 预后更差的生物标志物，当伴有 EMAST 时，可能是转移的预测因子。
