Genomic and micro-environmental insights into drug resistance in colorectal cancer liver metastases
Abstract Background Colorectal cancer (CRC) is known for its high heterogeneity, with liver metastases significantly impairing survival outcomes. Understanding the tumor microenvironment (TME) and genomic alterations in metastatic sites is crucial for developing personalized therapies that overcome...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-01976-8 |
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| _version_ | 1849767400823586816 |
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| author | Junjie Kuang Jun Li Siwei Zhou Yi Li Jinbo Lin Weizhen Huang Xia Yuan |
| author_facet | Junjie Kuang Jun Li Siwei Zhou Yi Li Jinbo Lin Weizhen Huang Xia Yuan |
| author_sort | Junjie Kuang |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer (CRC) is known for its high heterogeneity, with liver metastases significantly impairing survival outcomes. Understanding the tumor microenvironment (TME) and genomic alterations in metastatic sites is crucial for developing personalized therapies that overcome drug resistance and improve prognosis. Methods We profiled 54 CRC liver metastases, comparing them with 198 other metastatic lesions and normal liver tissues. By analyzing immune cell infiltration, stromal interactions, and key genomic alterations, we constructed an 11-gene prognostic model to predict survival and immunotherapy outcomes. Results CRC liver metastases with high-risk profiles demonstrated enriched follicular helper T cells, activated dendritic cells, and M2 macrophages in the TME. Frequent mutations in APC, TP53, KRAS, and PIK3CA were identified, alongside altered EGFR signaling. The 11-gene model effectively stratified patients by prognosis and predicted immunotherapy responses, emphasizing the therapeutic potential of targeting resistance mechanisms. Conclusions This study reveals how genomic and TME-driven factors contribute to drug resistance in CRC liver metastases. Integrating these insights with clinical data could advance precision therapies, addressing the evolving challenge of tumor drug resistance in CRC. |
| format | Article |
| id | doaj-art-d70bce9ff00b4522998b38b6f2d850da |
| institution | DOAJ |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-d70bce9ff00b4522998b38b6f2d850da2025-08-20T03:04:12ZengSpringerDiscover Oncology2730-60112025-02-0116111310.1007/s12672-025-01976-8Genomic and micro-environmental insights into drug resistance in colorectal cancer liver metastasesJunjie Kuang0Jun Li1Siwei Zhou2Yi Li3Jinbo Lin4Weizhen Huang5Xia Yuan6The Second Department of Oncology, Cancer Center, Huizhou First HospitalThe Second Department of Oncology, Cancer Center, Huizhou First HospitalThe Second Department of Oncology, Cancer Center, Huizhou First HospitalThe Second Department of Oncology, Cancer Center, Huizhou First HospitalThe Second Department of Oncology, Cancer Center, Huizhou First HospitalThe Second Department of Oncology, Cancer Center, Huizhou First HospitalThe Second Department of Oncology, Cancer Center, Huizhou First HospitalAbstract Background Colorectal cancer (CRC) is known for its high heterogeneity, with liver metastases significantly impairing survival outcomes. Understanding the tumor microenvironment (TME) and genomic alterations in metastatic sites is crucial for developing personalized therapies that overcome drug resistance and improve prognosis. Methods We profiled 54 CRC liver metastases, comparing them with 198 other metastatic lesions and normal liver tissues. By analyzing immune cell infiltration, stromal interactions, and key genomic alterations, we constructed an 11-gene prognostic model to predict survival and immunotherapy outcomes. Results CRC liver metastases with high-risk profiles demonstrated enriched follicular helper T cells, activated dendritic cells, and M2 macrophages in the TME. Frequent mutations in APC, TP53, KRAS, and PIK3CA were identified, alongside altered EGFR signaling. The 11-gene model effectively stratified patients by prognosis and predicted immunotherapy responses, emphasizing the therapeutic potential of targeting resistance mechanisms. Conclusions This study reveals how genomic and TME-driven factors contribute to drug resistance in CRC liver metastases. Integrating these insights with clinical data could advance precision therapies, addressing the evolving challenge of tumor drug resistance in CRC.https://doi.org/10.1007/s12672-025-01976-8Colorectal cancerLiver metastasisTumor microenvironmentGenomic alterationsDrug resistanceImmune therapy response |
| spellingShingle | Junjie Kuang Jun Li Siwei Zhou Yi Li Jinbo Lin Weizhen Huang Xia Yuan Genomic and micro-environmental insights into drug resistance in colorectal cancer liver metastases Discover Oncology Colorectal cancer Liver metastasis Tumor microenvironment Genomic alterations Drug resistance Immune therapy response |
| title | Genomic and micro-environmental insights into drug resistance in colorectal cancer liver metastases |
| title_full | Genomic and micro-environmental insights into drug resistance in colorectal cancer liver metastases |
| title_fullStr | Genomic and micro-environmental insights into drug resistance in colorectal cancer liver metastases |
| title_full_unstemmed | Genomic and micro-environmental insights into drug resistance in colorectal cancer liver metastases |
| title_short | Genomic and micro-environmental insights into drug resistance in colorectal cancer liver metastases |
| title_sort | genomic and micro environmental insights into drug resistance in colorectal cancer liver metastases |
| topic | Colorectal cancer Liver metastasis Tumor microenvironment Genomic alterations Drug resistance Immune therapy response |
| url | https://doi.org/10.1007/s12672-025-01976-8 |
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