克拉斯
结直肠癌
Wnt信号通路
PD-L1
癌症研究
微卫星不稳定性
医学
内科学
肿瘤科
癌症
基因
生物
遗传学
免疫疗法
等位基因
微卫星
作者
Qingqing Qiu,Dan Tan,Qiaofeng Chen,Ran Zhou,Xinqing Zhao,Wen Wang,Pengmin Yang,Jieyi Li,Zhongmiao Gong,Daoyun Zhang,Mingliang Wang
出处
期刊:PubMed
日期:2024-01-01
卷期号:14 (2): 796-808
摘要
The expression level of PD-L1 does not accurately predict the prognosis of advanced colorectal cancer (CRC) patients, but it still reflects the tumor microenvironment to some extent. By stratifying PD-L1 status, gene subtypes in PD-L1 positivity-related pathological pathways were analyzed for their relationship to MSI or TMB to provide more individualized treatment options for CRCs. A total of 752 advanced CRCs were included, and their genomic variance was measured by a targeted next generation sequencing panel in this study. MSI and TMB were both measured by NGS, while PD-L1 expression level was measured using the PD-L1 colon 22C3 pharmDx kit. We found RTK/RAS pathway was positively related to high PD-L1 expression, with BRAF V600E and most KRAS mutations (G12 and G13) subtypes showing a significant correlation. Conversely, the Wnt and p53 pathways were negatively related to high PD-L1 expression, with APC C-terminal alterations and other non-inactivation mutations in TP53 making a primary contribution with significant statistical significance. Major subtypes showing a significantly higher proportion of TMB-H or MSI-H were irrespective of PD-L1 status. These findings demonstrate pathological pathways associated with high PD-L1 expression, suggesting that pathway-induced oncogenic constructive PD-L1 upregulation may be the reason for the corresponding patients' primary resistance to immune checkpoint inhibitors (ICIs), rather than a lack of pre-existing immune responses.
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