Effect of RAS mutations and related immune characteristics on the prognosis of patients with MSI-H/dMMR colorectal cancer
Abstract Purpose Microsatellite high instability/deficient mismatch repair (MSI-H/dMMR) colorectal cancer (CRC) has an active tumor microenvironment, rendering it more sensitive to immune checkpoint inhibitors. Given that studies involving patients with MSI-H colorectal cancer with RAS mutations are...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03926-9 |
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| author | Yupeng Jiang Yuyao Liu Hong Huang Tiantian Zhao Zengyi Zhao Yawen Gao |
| author_facet | Yupeng Jiang Yuyao Liu Hong Huang Tiantian Zhao Zengyi Zhao Yawen Gao |
| author_sort | Yupeng Jiang |
| collection | DOAJ |
| description | Abstract Purpose Microsatellite high instability/deficient mismatch repair (MSI-H/dMMR) colorectal cancer (CRC) has an active tumor microenvironment, rendering it more sensitive to immune checkpoint inhibitors. Given that studies involving patients with MSI-H colorectal cancer with RAS mutations are scarce, we explored the effect of RAS mutations on the TME in patients with MSI-H/dMMR cancer and identified potential prognostic factors. Methods Seventy-five patients diagnosed with MSI-H/dMMR colorectal cancer were retrospectively enrolled and divided into RAS-mutant and -wild-type groups. The expression levels of CD11c+ dendritic cells, CD4+ T cells, CD8+ T cells, and regulatory T cell (Treg) markers were detected, and prognostic factors were analyzed. Results RAS-mutant MSI-H colorectal patients were more likely to have: (1) higher platelet values; (2) shorter disease-free survival (DFS); (3) lower infiltrated numbers of CD11c+ dendritic cells, CD4+ T lymphocytes, and CD8+ T lymphocytes, and higher infiltrated numbers of Foxp3+ Treg cells. In MSI-H/dMMR CRC patients: (1) the high CD11c + , CD4 +, and CD8 + cells infiltration group had longer DFS than the low-infiltration group, and Foxp3 + cells infiltration was not significantly correlated with DFS; (2) the RAS mutation status, number of CD11c+ cells infiltrated, and carbohydrate antigen 19–9 (CA19–9) level were the potential prognostic factors. Conclusion RAS mutations in patients with MSI-H/dMMR CRC may reduce the infiltration of CD11c+ dendritic cells, CD4+ T cells, and CD8+ T cells, and increase the infiltration of Foxp3+ Treg cells to affect the tumor microenvironment of patients. RAS gene status, CD11c + cells infiltration, and CA19–9 level were potential prognostic factors for MSI-H/dMMR CRC. |
| format | Article |
| id | doaj-art-470db0eadf01471fb547041677f30e06 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-470db0eadf01471fb547041677f30e062025-02-02T12:26:15ZengSpringerCancer Immunology, Immunotherapy1432-08512025-02-0174311410.1007/s00262-024-03926-9Effect of RAS mutations and related immune characteristics on the prognosis of patients with MSI-H/dMMR colorectal cancerYupeng Jiang0Yuyao Liu1Hong Huang2Tiantian Zhao3Zengyi Zhao4Yawen Gao5Department of Oncology, The Second Xiangya Hospital, Central South UniversityDepartment of Oncology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaGuilin Medical UniversityDepartment of Oncology, The Second Xiangya Hospital, Central South UniversityDepartment of Oncology, The Second Xiangya Hospital, Central South UniversityDepartment of Oncology, The Second Xiangya Hospital, Central South UniversityAbstract Purpose Microsatellite high instability/deficient mismatch repair (MSI-H/dMMR) colorectal cancer (CRC) has an active tumor microenvironment, rendering it more sensitive to immune checkpoint inhibitors. Given that studies involving patients with MSI-H colorectal cancer with RAS mutations are scarce, we explored the effect of RAS mutations on the TME in patients with MSI-H/dMMR cancer and identified potential prognostic factors. Methods Seventy-five patients diagnosed with MSI-H/dMMR colorectal cancer were retrospectively enrolled and divided into RAS-mutant and -wild-type groups. The expression levels of CD11c+ dendritic cells, CD4+ T cells, CD8+ T cells, and regulatory T cell (Treg) markers were detected, and prognostic factors were analyzed. Results RAS-mutant MSI-H colorectal patients were more likely to have: (1) higher platelet values; (2) shorter disease-free survival (DFS); (3) lower infiltrated numbers of CD11c+ dendritic cells, CD4+ T lymphocytes, and CD8+ T lymphocytes, and higher infiltrated numbers of Foxp3+ Treg cells. In MSI-H/dMMR CRC patients: (1) the high CD11c + , CD4 +, and CD8 + cells infiltration group had longer DFS than the low-infiltration group, and Foxp3 + cells infiltration was not significantly correlated with DFS; (2) the RAS mutation status, number of CD11c+ cells infiltrated, and carbohydrate antigen 19–9 (CA19–9) level were the potential prognostic factors. Conclusion RAS mutations in patients with MSI-H/dMMR CRC may reduce the infiltration of CD11c+ dendritic cells, CD4+ T cells, and CD8+ T cells, and increase the infiltration of Foxp3+ Treg cells to affect the tumor microenvironment of patients. RAS gene status, CD11c + cells infiltration, and CA19–9 level were potential prognostic factors for MSI-H/dMMR CRC.https://doi.org/10.1007/s00262-024-03926-9RAS mutationHigh microsatellite instabilityDeficient mismatch repairColorectal cancerTumor microenvironment |
| spellingShingle | Yupeng Jiang Yuyao Liu Hong Huang Tiantian Zhao Zengyi Zhao Yawen Gao Effect of RAS mutations and related immune characteristics on the prognosis of patients with MSI-H/dMMR colorectal cancer Cancer Immunology, Immunotherapy RAS mutation High microsatellite instability Deficient mismatch repair Colorectal cancer Tumor microenvironment |
| title | Effect of RAS mutations and related immune characteristics on the prognosis of patients with MSI-H/dMMR colorectal cancer |
| title_full | Effect of RAS mutations and related immune characteristics on the prognosis of patients with MSI-H/dMMR colorectal cancer |
| title_fullStr | Effect of RAS mutations and related immune characteristics on the prognosis of patients with MSI-H/dMMR colorectal cancer |
| title_full_unstemmed | Effect of RAS mutations and related immune characteristics on the prognosis of patients with MSI-H/dMMR colorectal cancer |
| title_short | Effect of RAS mutations and related immune characteristics on the prognosis of patients with MSI-H/dMMR colorectal cancer |
| title_sort | effect of ras mutations and related immune characteristics on the prognosis of patients with msi h dmmr colorectal cancer |
| topic | RAS mutation High microsatellite instability Deficient mismatch repair Colorectal cancer Tumor microenvironment |
| url | https://doi.org/10.1007/s00262-024-03926-9 |
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