Elevated Expression of ADAP2 is Associated With Aggressive Behavior of Human Clear-Cell Renal Cell Carcinoma and Poor Patient Survival.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. ADAP2 is a GTPase-activating protein was upregulated in clear cell renal cell carcinoma. The role of ADAP2 in ccRCC progression is unknown. ADAP2 expression in ccRCC cell lines and tissues was examined via real-time PCR, Western blot and IHC. MTS, colony formation and transwell assay to explore the role of ADAP2 in ccRCC. ADAP2 in growth and metastasis of ccRCC were evaluated in vivo through ccRCC xenograft tumor growth, lung metastatic mice model. The prognostic role of ADAP2 was evaluated by survival analysis. ADAP2 mRNA was expressed at significantly higher levels in 23 pairs of ccRCC tissues than in normal kidney tissues (P < 0.01). Immunohistochemical analysis of 298 ccRCC tissues revealed elevated ADAP2 expression as an independent unfavorable prognostic factor for the overall survival (P = 0.0042) and progression-free survival (P = 0.0232) of patients. The KaplanMeier survival curve showed that patients with a higher expression of ADAP2 showed a significantly lower overall survival rate and disease-free survival rate. Moreover, high expression of ADAP2 at the mRNA level was associated with a worse prognosis for overall survival (P = 0.0083) in The Cancer Genome Atlas (TCGA) cohort. In vivo and in vitro functional study showed that overexpression of ADAP2 promotes ccRCC cell proliferation and metastasis ability, whereas knockdown of ADAP2 inhibited cell proliferation, colony formation, migration and invasion. ADAP2 is a novel prognostic marker and could promotes tumor progression in ccRCC.