The significance of TIMD4 expression in clear cell renal cell carcinoma.

T-cell immunoglobulin and mucin domain (TIMD) family genes are related to innate immune responses. TIMD4 is a receptor for phosphatidylserine and is involved in the phagocytosis of apoptotic cells by macrophages. In the present study, we found that TIMD4 is expressed on the cancer cells of patients with clear cell renal cell carcinoma (ccRCC). TIMD4 was immunostained in the resected samples of 89 patients diagnosed as ccRCC. High expression of TIMD4 in cancer cells was closely related to short progression free survival time; however, it was not correlated with other clinicopathological factors. Intracellular expression of TIMD4 was observed in the RCC cell line, 786-O. In vitro studies using 786-O cells and shRNA targeting TIMD4 indicated that TIMD4 expression was associated with resistance to sorafenib but not with cell proliferation. TIMD4 might be useful as a prognostic factor and may also be a new target for therapy of ccRCC.