Fig. 1: KIAA1199 overexpression establishes a hepatic pre-metastatic niche driving colorectal cancer liver metastasis.

A KIAA1199 expression in metastatic (M, n = 67 patients) versus non-metastatic (NM, n = 353 patients) CRC samples from TCGA cohort. Expression is significantly higher in the metastatic group (unpaired t test). B Kaplan–Meier cumulative incidence curve and Cox regression analysis of TCGA-CRC patients stratified by KIAA1199 expression (high: top 20%, n = 95; low: bottom 20%, n = 96). High KIAA1199 expression correlates with a significantly increased risk of disease progression (log-rank test). C Representative immunohistochemical (IHC) staining of KIAA1199 in CRC tissue microarrays (left). Corresponding MRI scans (right) track liver metastasis progression in patients from diagnosis (0 months) to 12- and 18-month follow-up (n = 104 patients). White arrows: baseline lesions; Red arrowheads: new lesions; Red dashed lines: maximum diameter of metastatic progression. Scale bars: 100 µm (IHC) and 1 cm (MRI). D Proportion of patients with distant metastasis in KIAA1199-low (n = 63 patients) versus KIAA1199-high (n = 41 patients) groups based on IHC scoring. The high-expression group showed a significantly higher metastatic rate (63% vs. 36%; Chi-square test). E Kaplan–Meier curves of cumulative liver metastasis incidence stratified by KIAA1199 expression (n = 104 patients, log-rank test). F Representative H&E staining (left) and spatial transcriptomic maps (right) showing KIAA1199 distribution in primary CRC (top) and matched CRLM (bottom) (n = 2 patients). Red dashed lines delineate tumor areas. Scale bars: 200 µm. G Schematic of the dual-tumor experimental timeline. BALB/c mice received orthotopic implantation of CT26 cells (KIAA1199 OE/KD or controls) on day 0. On day 7, wild-type CT26 cells were injected intrasplenically to mimic dissemination, followed by splenectomy 15 min later. Analysis was performed on day 21. H Representative gross liver images and H&E staining showing metastatic burden (n = 5 mice). Scale bars: 2 mm (gross) and 2 mm (histology). I–K Quantification of relative liver weight (I), number of metastatic nodules (J), and metastatic area percentage (K) (n = 5 mice, Student’s t test). L Schematic of the survival study workflow. Orthotopic implantation (KIAA1199 OE/KD or controls) was followed by intrasplenic injection on day 7. Survival was monitored until day 60. M Kaplan–Meier survival curves (n = 10 mice, log-rank test). All statistical tests are two-sided. Data are presented as mean ± s.d. Source data and exact p values are provided as a Source Data file.