结直肠癌微卫星不稳定性检测的应用与挑战

Application and challenge of microsatellite instability detection in colorectal cancer

结直肠癌是常见的消化道恶性肿瘤之一,我国结直肠癌的发病率及死亡率仍呈上升趋势。探究结直肠癌发生、发展的分子机制具有重要意义。微卫星是遍布于基因组中的短串联重复序列,微卫星不稳定性(MSI)检测在结直肠癌的临床诊断与治疗中具有重要价值。MSI检测是Lynch综合征筛查的重要方法。对于Ⅱ期结直肠癌患者,MSI状态是术后复发的影响因素,亦是辅助治疗的重要参考依据。对于Ⅳ期结直肠癌患者,MSI状态是筛查免疫检查点抑制剂适用人群的重要指标。然而,MSI的应用仍然存在一系列问题。MSI检测方法并未完全统一,MSI检测对象的要求具有普遍性但缺乏精准性,MSI对预后的预测作用不足,MSI对化疗、免疫治疗疗效的判断作用不足。此外,随着其他相关分子靶标,如程序性细胞死亡受体1、程序性细胞死亡受体配体1、肿瘤突变负荷、免疫评分等的临床应用,MSI在结直肠癌中的应用价值面临挑战,有待更多研究深入挖掘。笔者就MSI检测及应用存在的问题进行探讨,旨在为临床实践提供参考。

Colorectal cancer(CRC)is one of the most common gastrointestinal cancers.The incidence and mortality of CRC are still rising in China.It is of great importance to explore the molecular mechanisms of the development and progression of CRC.Microsatellites are short tandem repeats that are distributed throughout the genome.Detection of microsatellite instability(MSI)is of great value in the diagnosis and treatment of CRC.MSI detection is an important method for Lynch syndrome screening.For patients with stageⅡCRC,MSI status is an influencing factor for postoperative recurrence and an important reference for adjuvant therapy.For patients with stageⅣCRC,MSI status is an important indicator for screening potential patients suitable for treatment of immune checkpoint inhibitors.However,there are still problems concerning the application of MSI.The detection methods of MSI have not been fully unified.The requirement of MSI detection in CRC patients are universal but not precise.MSI is not a valid predictor for the prognosis of CRC patients,and it could not effectively predict the efficacy of chemotherapy and immunotherapy.Moreover,with the application of other molecular markers,such as programmed death‐1,programmed death‐ligand 1,tumor mutation burden and immunoscore,the value of MSI in CRC is being challenged and remains to be unveiled with more studies.The authors investigate the problems in MSI detection and application,in order to provide reference for clinical practice.