Abstract: Objective To analyze the forkhead box L2 neighbor (FOXL2NB) expression in colorectal cancer (CRC) and its potential clinical significance, and to explore the role of FOXL2NB in CRC cells. Methods Real time qPCR and Western blot were used to analyze the expression of FOXL2NB in CRC tissues and cells. Transwell and CCK-8 assay were used to investigate the effect of FOXL2NB on the proliferation and migration in SW620 cell line. Kaplan-Meier and multivariate Cox regression analysis were used to evaluate the prognostic significance of FOXL2NB in CRC patients. CIBERSORT R package was used to calculate the correlation between FOXL2NB expression and immune cell infiltration in CRC tissues. limma R package was used to calculate the genes that significantly correlated with FOXL2NB expression. Results The mRNA and protein levels of FOXL2NB were significantly increased in CRC cell lines and tissues (P＜ 0.05). High level of FOXL2NB was associated with shorter overall survival and progression free survival in CRC patients (P＜ 0.05), which could be used as an independent risk factor for CRC prognosis (HR=2.27, 95% CI=1.78-2.9, P＜ 0.001). FOXL2NB knockdown inhibited the migration and proliferation of CRC cells. Cell adhesion molecules and tumor immune-related pathways were significantly enriched in CRC with high FOXL2NB expression, CD8⁺ T cells and activated dendritic cells were significantly increased, while M0 macrophages were significantly decreased. FOXL2NB expression was positively correlated with SCRT2, MGAT5B, SELENOV, FOXB1, KCNA4, LRRC14B and SLC32A1 genes. Conclusions FOXL2NB is highly expressed in CRC and potentially predicts poor prognosis. FOXL2NB might promote CRC cell proliferation and migration.

Key words: colorectal cancer, forkhead box, FOXL2NB, cell adhesion, tumor immunity