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Updated: Jan 7, 2026
Mining Spatial Transcriptomics Datasets using DeepSpaceDB
Published on: September 5, 2025
Single-cell and spatial transcriptome profiling identifies the immunosuppressive spatial niche in KRAS-mutant
Sheng Yang1,2, Chao Gu3, Xinsheng Miao3
1Department of General Surgery, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, China.
Background:
KRAS is one of the most frequently mutated genes in colorectal cancer (CRC) and plays a crucial role in tumorigenesis, progression, immune evasion, and treatment resistance. The pronounced heterogeneity within KRAS-mutant CRC highlights the urgent need for more precise and personalized therapeutic approaches.
Methods:
To investigate this heterogeneity, we employed single-cell RNA sequencing and spatial transcriptomics to comprehensively characterize the tumor microenvironment of KRAS-mutant CRC. Data preprocessing and clustering were performed using Scanpy. Spatial cell-type deconvolution was conducted via Cell2location, whereas intercellular communication and spatial dependencies were analyzed using CellChat, MISTy, and stLearn.
Results:
Our analyses revealed that KRAS-mutant tumor epithelial cells recruit Mono_S100A8 monocytes via the MDK_SDC4 signaling axis. Concurrently, surrounding Fib_CTHRC1 fibroblasts secrete collagen, which interacts with integrin receptors on KRAS-mutant epithelial cells and contributes to the exclusion of lymphocyte infiltration.
Conclusion:
These cellular components collaboratively established an immunosuppressive spatial niche. These findings offer novel theoretical insights and potential targets for the development of immunoregulatory strategies tailored to KRAS-mutant CRC.
