biostudies-literatureUnknown14(2)Qiu QThe 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 <i>BRAF V600E</i> and most <i>KRAS</i> mutations (G12 and G13) subtypes showing a significant correlation. Conversely, the Wnt and p53 pathways were negatively related to high PD-L1 expression, with <i>APC</i> C-terminal alterations and other non-inactivation mutations in <i>TP53</i> 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.American journal of cancer research796-808https://www.ebi.ac.uk/biostudies/studies/S-EPMC10915335biostudies-literatureClinical implications of PD-L1 expression and pathway-related molecular subtypes in advanced Asian colorectal cancer patients.PMC10915335Wang MChen QLi JZhang DZhou RQiu QTan DYang PGong ZWen WZhao XfalseClinical implications of PD-L1 expression and pathway-related molecular subtypes in advanced Asian colorectal cancer patients.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 <i>BRAF V600E</i> and most <i>KRAS</i> mutations (G12 and G13) subtypes showing a significant correlation. Conversely, the Wnt and p53 pathways were negatively related to high PD-L1 expression, with <i>APC</i> C-terminal alterations and other non-inactivation mutations in <i>TP53</i> 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.2024-01-01T00:00:00Z20242026-05-29T12:06:02.009Z2024-11-20T23:50:17.262ZS-EPMC109153353845541410.62347/fssf9938