Abstract
Colorectal cancer (CRC) remains a major global health challenge, underscoring the need for reliable biomarkers to improve prognosis and therapeutic stratification. In this study, we comprehensively investigated the expression pattern, clinical significance, molecular functions, and immunological implications of LINGO1 in CRC. Integrative analyses of TCGA and GEO datasets, together with validation in 72 clinical CRC samples, demonstrated that LINGO1 is markedly overexpressed in tumors and strongly associated with advanced clinicopathological features and poor patient outcomes. Functional experiments revealed that both knockdown of LINGO1 in SW480 and LoVo cells and overexpression of LINGO1 in HCT116 cells significantly modulate malignant phenotypes, including proliferation, migration, invasion, and angiogenic capacity. Transcriptome-wide and pathway enrichment analyses further indicated that high LINGO1 expression is linked to epithelial–mesenchymal transition, angiogenesis, Wnt/β-catenin signaling, and other oncogenic pathways. Immunogenomic profiling, supported by multiplex immunofluorescence staining, showed that elevated LINGO1 is associated with an immunosuppressive tumor microenvironment characterized by reduced CD8⁺ T-cell infiltration and diminished GZMB expression, alongside upregulation of multiple immune checkpoint molecules. Collectively, our findings identify LINGO1 as a novel oncogenic driver and immune-modulatory biomarker in colorectal cancer, with potential value for prognosis and therapeutic targeting.
Data availability
The datasets used or analyzed during the current study are detailed in the Methods section. Further inquiries can be directed to the corresponding authors upon reasonable request.
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Manuscript preparation: PM, ZS, XL. Data analysis: PM. Data analysis assistant: ZS, PCY. Background investigation: PM, ZS, FZY. Data collection: FZY, PCY. Experiment execution: PM, XL, FZY, PCY. Project designation, funding and supervision: PM, XL, ZS. All authors contributed to the article and approved the submitted version.
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This study was approved by the Institutional Review Board (IRB) of the Affiliated Hospital of Nantong University. Written informed consent was obtained from all participants, and all methods were carried out in accordance with relevant guidelines and regulations. The study complies with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. For animal experiments, all procedures were conducted in compliance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines, the Guidance on the operation of the Animals (Scientific Procedures) Act 1986, EU Directive 2010/63/EU for the protection of animals used for scientific purposes, and the NIH Guide for the Care and Use of Laboratory Animals, or equivalent internationally recognized bodies. The study was approved by the Institutional Animal Care and Use Committee (IACUC) of the Affiliated Hospital of Nantong University, and all efforts were made to minimize animal suffering.
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Ma, P., Yao, F., Yue, P. et al. Transcriptional activation of LINGO1 facilitates proliferation and immune escape in colorectal cancer. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38760-9
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DOI: https://doi.org/10.1038/s41598-026-38760-9
