CXCR1 expression predicts benefit from tyrosine kinase inhibitors therapy in patients with metastatic renal cell carcinoma

Purpose

CXCR1 signaling promotes tumor progression in various cancers, and clinical trial has proved efficacy of CXCR1 inhibitor in metastatic breast cancer. Therefore, we investigated the prognostic value of CXCR1 in patients with metastatic renal cell carcinoma (mRCC) receiving tyrosine kinase inhibitors (TKIs) therapy.

Materials and Methods

Patients treated with sunitinib or sorafenib were retrospectively enrolled (n = 111). CXCR1 expression was assessed by immunohistochemical staining of tissue microarrays of primary tumor, and its association with prognosis and therapeutic response were evaluated. To explore possible mechanism related to CXCR1 expression, gene set enrichment analysis was performed based on The Cancer Genome Atlas cohort.

Results

High CXCR1 expression was associated with poorer overall survival (P = 0.015) and was an independent prognostic factor for patients with mRCC treated by TKIs (Hazard Ratio = 1.683, 95% Confidence Interval: 1.109–2.553, P = 0.014). CXCR1 expression was also associated with worse therapeutic response of TKIs (P = 0.017). Thirteen pathways, including hypoxia and angiogenesis, were identified to be enriched in CXCR1 positive patients.

Conclusions

High CXCR1 expression indicates reduced benefit from TKIs therapy in patients with mRCC. The mechanism may be attributed to the enriched pathways of hypoxia and angiogenesis in CXCR1 positive patients. CXCR1 may be a potential therapeutic target for mRCC, but further studies are required.