Screening novel targets for combination immunotherapy of colorectal cancer based on cancer immune cycle

ZENG Wei; TANG Jubin; CHEN Xiangzhou; CHEN Wei; YANG Dan; ZHU Jinfeng

doi:10.16766/j.cnki.issn.1674-4152.003829

Volume 23 Issue 1

Jan. 2025

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Article Navigation > Chinese Journal of General Practice > 2025 > 23(1): 31-35

ZENG Wei, TANG Jubin, CHEN Xiangzhou, CHEN Wei, YANG Dan, ZHU Jinfeng. Screening novel targets for combination immunotherapy of colorectal cancer based on cancer immune cycle[J]. Chinese Journal of General Practice, 2025, 23(1): 31-35. doi: 10.16766/j.cnki.issn.1674-4152.003829

Citation:

ZENG Wei, TANG Jubin, CHEN Xiangzhou, CHEN Wei, YANG Dan, ZHU Jinfeng. Screening novel targets for combination immunotherapy of colorectal cancer based on cancer immune cycle[J]. Chinese Journal of General Practice, 2025, 23(1): 31-35. doi: 10.16766/j.cnki.issn.1674-4152.003829

Citation:

ZENG Wei, TANG Jubin, CHEN Xiangzhou, CHEN Wei, YANG Dan, ZHU Jinfeng. Screening novel targets for combination immunotherapy of colorectal cancer based on cancer immune cycle[J]. Chinese Journal of General Practice, 2025, 23(1): 31-35. doi: 10.16766/j.cnki.issn.1674-4152.003829

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Screening novel targets for combination immunotherapy of colorectal cancer based on cancer immune cycle

doi: 10.16766/j.cnki.issn.1674-4152.003829

1.
The Forth Department of Cancer Center, the Sixth Affiliated Hospital of South China University of Technology, Foshan, Guangdong 528200, China

Funds:

82103636

2022A1515012613

Received Date: 2024-04-30
Available Online: 2025-02-13

Abstract

Abstract

Objective At this stage, immune checkpoint inhibitors (ICIs) are approved for the treatment of colorectal cancer. However, about 50% of dMMR/MSI-H-type patients are primarily resistant to ICIs, and MSS/pMMR-type patients have limited response to single-agent ICIs; therefore, there is an urgent need to find new targets for immune-combination therapy to further improve the therapeutic efficacy of ICIs in patients. Methods In this study, we combined the Cancer Immune Cycle Score with the weighted gene co-expression network and systematic analyses to screen immunosuppressive genes in colorectal cancer; analyzed gene expression profiles in colorectal cancer tissues using the GEPIA2 database; CIBERSORT assessed the correlation between gene expression and the level of immune cell infiltration; the TIDE algorithm predicted the gene expression in relation to the efficacy of patient immunotherapy relationship; Kaplan-Meier survival analysis to compare the prognostic differences between groups with high and low expression levels of genes after receiving immunotherapy; and GSEA to analyze the regulatory mechanisms of genes involved in colorectal cancer genesis, development, and affecting the prognosis of patients. Results Cancer immune cycle score with weighted gene co-expression network and systematic analysis showed that DDX27 was an immunosuppressive target of colorectal cancer; DDX27 was significantly highly expressed in colorectal cancer tissues (P < 0.001), which was positively correlated with the patients ' later N stage (P=0.005), TNM stage (P=0.006) and infiltration level of suppressive immune cells; patients in the group with high levels of DDX27 expression were poorly treated with immunotherapy, and the overall survival of patients in this group treated with ICI was shorter than that in the group with low levels of DDX27 expression (7.2 months vs. 9.6 months); further analysis showed that DDX27 might be involved in the occurrence and development of colorectal cancer through the regulation of RNA processing and metabolism, and affect the prognosis of patients. Conclusion Targeting DDX27 may be a new target for immunotherapy of colorectal cancer by inhibiting the infiltration of immunosuppressive cells and interfering with tumorigenesis and development.
- Colorectal cancer,
- Cancer immune cycle,
- Immunotherapy

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Screening novel targets for combination immunotherapy of colorectal cancer based on cancer immune cycle

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