SPP1 and cancer: Since high SPP1 expression in primary CRC tumors was previously associated with poor prognosis [44] and SFRP2 promoter methylation resulting in reduced SFRP2 expression was considered a CRC biomarker [45], the expression during the course of cancer progression was analyzed in paired normal (N), P and M samples of the REVEAL study (n = 9) (Figure 8E,F).