As SMOC2 is enriched in the stem cells of the intestinal crypts, we examined whether there is any correlation between SMOC2 and other ISC markers, including LGR5, ASCL2, EPHB2, and OLFM4. We found that only OLFM4 demonstrated a positive association with SMOC2 (r2 = 0.15, P = 0.04) (Fig. 1c), suggesting that the close relationship between ISC signature genes observed in the normal stem cell niche is disrupted during cancer development. This evidence concerns the gene EPHB2 and cancer.