Abstract
Chemokines are important in the development and progression of tumors. We investigated the expression of CXCL14 and CXCL16 in colon cancer. Expression of mRNA was assessed in primary tumors and lymph nodes and CXCL16 mRNA levels were correlated to patient’s survival. Protein expression was investigated by two-color immunofluorescence and immunomorphometry. CXCL14 and CXCL16 mRNA levels and protein expression were significantly higher in colon cancer primary tumors compared to apparently normal colon tissue. Positive cells were tumor cells, as revealed by anti-CEA and anti-EpCAM staining. CXCL16, but not CXCL14, mRNA levels were significantly higher in hematoxylin and eosin positive (H&E(+)) compared to H&E(−) colon cancer lymph nodes or control nodes (P < 0.0001). CXCL16 mRNA was expressed in 5/5 colon cancer cell lines while CXCL14 was expressed significantly in only one. Kaplan-Meier analysis revealed that colon cancer patients with lymph nodes expressing high or very high levels (7.2 and 11.4 copies/18S rRNA unit, respectively) of CXCL16 mRNA had a decreased mean survival time of 30 and 46 months at the 12-year follow-up (P = 0.04, P = 0.005, respectively). In conclusion, high expression of CXCL16 mRNA in regional lymph nodes of colon cancer patients is a sign of a poor prognosis.
Highlights
Chemokines constitute a superfamily of chemotactic cytokines that bind to receptors belonging to class A G-protein-coupled receptors, which trigger signaling cascades and promote multiple cellular functions [1]
While there was a significant difference between H&E(+) lymph nodes and H&E(−) lymph nodes and controls for CXCL16 mRNA (P = 0.05 and P = 0.02, respectively), no difference between the three lymph node groups was seen for CXCL14. These results suggest that CXCL16 mRNA expression, in contrast to CXCL14 mRNA, may act as a biomarker for poor prognosis
If the group of patients subjected to analysis only included those that had a positive carcinoembryonic antigen (CEA) mRNA value, e.g., the CEA(int) plus CEA(+) group and using the CXCL16 mRNA cut-off level of 11.4, the recurrence rate was further increased to 2.9 folds at five years and 3.2-fold at 12 years (P = 0.01 and P = 0.005, respectively) and mean survival time decreased by 11 months at five years and 56 months at 12 years (P = 0.008 and P = 0.003, respectively) when compared to the CXCL16(−−) group (Figure 4D and Table 1)
Summary
Chemokines constitute a superfamily of chemotactic cytokines that bind to receptors belonging to class A G-protein-coupled receptors, which trigger signaling cascades and promote multiple cellular functions [1]. If the group of patients subjected to analysis only included those that had a positive CEA mRNA value, e.g., the CEA(int) plus CEA(+) group and using the CXCL16 mRNA cut-off level of 11.4, the recurrence rate was further increased to 2.9 folds at five years and 3.2-fold at 12 years (P = 0.01 and P = 0.005, respectively) and mean survival time decreased by 11 months at five years and 56 months at 12 years (P = 0.008 and P = 0.003, respectively) when compared to the CXCL16(−−) group (Figure 4D and Table 1).
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