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METHODS FOR PREDICTING THE SURVIVAL TIME OF PATIENTS SUFFERING FROM A MICROSATELLITE STABLE COLORECTAL CANCER

机译:预测微卫星稳定大肠癌患者生存时间的方法

摘要

The present invention relates to methods for predicting the survival time of patients suffering from a microsatellite stable colorectal cancer. The inventors performed bivariate Cox models for analyzing the impact of stimulatory/Inhibitory immune checkpoint (ICK) expression on the survival of patients suffering from colorectal cancers (CMS1, CMS2, CMS3, CMS4, and MSI) in 2 cohorts (CIT and TCGA) or when the corhorts are combined. The inventors demonstrated that the metagenes corresponding to ICKs, cytotoxic T-cell lymphocytes (CTL), cytotoxicity and Th1 orientation were overexpressed in MSS tumors belonging to CMS1 and CMS4 as compared to MSS CRC from CMS2 and CMS3 demonstrating their prognostic value. Thus, the invention relates to a method for predicting the survival time of a patient suffering from a microsatellite stable colorectal cancer belonging to consensus molecular subtypes CMS1 and CMS4 comprising i) determining the expression level of at least one gene encoding for an immune checkpoint protein in a tumor tissue sample obtained from the patient, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) concluding that the patient will have a long survival time when the level determined at step i) is lower than the predetermined reference value or concluding that the patient will have a short survival time when the level determined at step i) is higher than the predetermined reference value.
机译:本发明涉及预测患有微卫星稳定结直肠癌的患者的生存时间的方法。发明人进行了双变量Cox模型分析了两个队列(CIT和TCGA)中刺激/抑制性免疫检查点(ICK)表达对大肠癌(CMS1,CMS2,CMS3,CMS4和MSI)患者生存的影响,或者当这些人合在一起时。发明人证明,与来自CMS2和CMS3的MSS CRC相比,在属于CMS1和CMS4的MSS肿瘤中与ICKs,细胞毒性T细胞淋巴细胞(CTL),细胞毒性和Th1方向相对应的基因表达过度表达,证明了它们的预后价值。因此,本发明涉及预测属于共有分子亚型CMS1和CMS4的,属于微卫星稳定结直肠癌的患者的生存时间的方法,该方法包括:i)确定至少一种编码免疫检查点蛋白的基因的表达水平。从患者获得的肿瘤组织样品,ii)将步骤i)中确定的表达水平与预定参考值进行比较,并且iii)结论是,如果步骤i)中确定的水平低于标准水平,则患者将具有较长的生存时间。预定参考值或结论,即在步骤i)中确定的水平高于预定参考值时,患者将具有较短的生存时间。

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