Tumor location determines midkine level and its association with the disease progression in colorectal cancer patients: a pilot study

PURPOSE: The purpose of this study was to evaluate midkine, multipotential cytokine, and growth factor in colorectal cancer (CRC) stratified by tumor location. METHODS: Midkine was assessed immunoenzymatically in paired cancerous and noncancerous tissues from 53 CRCs and referred to CRC stage, tumor location, and size, and circulating cytokine levels. RESULTS: Midkine was higher in cancerous versus noncancerous tissue in 98 % cases (424.2 vs. 31.1 pg/mg, p < 0.0001). Mean fold increase was 30.1; in 72.5 %, the relative increase was over fivefold. Midkine upregulation was more pronounced in colon than in rectum (fold increase: 36.6 vs. 12.7, p = 0.005) due to higher midkine level in noncancerous rectal than colonic tissue (45.5 vs. 26.2 pg/mg, p = 0.074). Tumor location affected midkine association with CRC stage. Midkine fold change was higher in advanced stages of rectal cancers (16.8 vs. 5.3, respectively in III/IV vs. I/II, p = 0.013), while it tended to be lower in colonic ones (25.3 vs. 47.8, p = 0.134). In addition, fold change in midkine level was higher in rectal N1 than N0 cancers (17.3 vs. 16.5, p = 0.032), while it tended to be lower in colonic cancers (23.6 vs. 50.1, p = 0.085). Midkine negatively correlated with tumor size (r = 0.40, p = 0.017), while it tended to positively correlate with its serum levels (r = 0.45, p = 0.081). CONCLUSIONS: Midkine is differently expressed in tumors arising from colonic and rectal mucosa, where it may play diverse roles in carcinogenesis. High midkine expression in noncancerous rectal mucosa might contribute to, a characteristic for rectal cancers, higher incidence of local recurrence. Divergent expression of midkine and its association pattern ought to be taken into account while designing midkine-directed therapies for CRC.