Altered Expression of DDR1 in Clear Cell Renal Cell Carcinoma Correlates With miR-199a/b-5p and Patients' Outcome.

BACKGROUND/AIM: Accumulating evidence suggests that discoidin domain receptor tyrosine kinase 1 (DDR1) has an oncogenic role. Therefore, the aim of this study was to evaluate the potential utility of DDR1 and its post-transcriptional repressors, miR-199a-5p and miR-199b-5p, as prognostic factors in clear cell renal cell carcinoma (ccRCC).

PATIENTS AND METHODS

The expression of DDR1 in tumor and normal renal tissues of 56 patients with ccRCC was assessed by reverse transcription quantitative polymerase chain reaction, western blotting and immunohistochemistry. Renal cancer cells were transfected with specific RNA sequences to validate DDR1 as a putative miR-199a/b-5p target.

RESULTS

Decreased DDR1 mRNA and protein, as well as miR-199a/b-5p levels were found in ccRCC. Low DDR1 protein was associated with higher nuclear grade and shorter overall survival. DDR1 immunoreactivity was elevated in the nuclei and unchanged in the membrane/cytoplasmic compartment of tumor cells. DDR1 levels correlated with those of miR-199a/b-5p. In addition, we validated DDR1 as a target gene for miR-199a/b-5p in renal cancer cell lines.

CONCLUSION

DDR1 expression is altered in ccRCC, but our findings do not support its oncogenic role. In-depth investigation will be necessary to elucidate the exact role and potential utility of miR-199a/b-5p in ccRCC.