微卫星不稳定性
结直肠癌
肿瘤科
内科学
医学
癌症
免疫系统
免疫疗法
林奇综合征
基因
DNA错配修复
癌症研究
微卫星
生物
免疫学
等位基因
遗传学
作者
Can Lu,Xiaopeng Zhang,Josefine Schardey,Ulrich Wirth,Kathrin Heinrich,Luca Massiminio,Giulia Martina Cavestro,Jens Neumann,Alexandr V. Bazhin,Jens Werner,Florian Kühn
标识
DOI:10.1038/s41698-023-00414-8
摘要
Abstract The incidence of early-onset colorectal cancer (EO-CRC, in patients younger than 50) is increasing worldwide. The specific gene signatures in EO-CRC patients are largely unknown. Since EO-CRC with microsatellite instability is frequently associated with Lynch syndrome, we aimed to comprehensively characterize the tumor microenvironment (TME) and gene expression profiles of EO-CRC with microsatellite stable (MSS-EO-CRC). Here, we demonstrated that MSS-EO-CRC has a similar pattern of tumor-infiltrating immune cells, immunotherapeutic responses, consensus molecular subtypes, and prognosis as late-onset CRC with MSS (MSS-LO-CRC). 133 differential expressed genes were identified as unique gene signatures of MSS-EO-CRC. Moreover, we established a risk score, which was positively associated with PD-L1 expression and could reflect both the level of tumor-infiltrating immune cells and the prognosis of MSS-EO-CRC patients. Application of this score on the anti-PD-L1 treatment cohort demonstrated that the low-risk score group has significant therapeutic advantages and clinical benefits. In addition, candidate driver genes were identified in the different-sidedness of MSS-EO-CRC patients. Altogether, MSS-EO-CRC exhibits distinct molecular profiles that differ from MSS-LO-CRC even though they have a similar TME characterization and survival pattern. Our risk score appears to be robust enough to predict prognosis and immunotherapeutic response and therefore could help to optimize the treatment of MSS-EO-CRC.
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