Heme oxygenase-1 is a predictive biomarker for therapeutic targeting of advanced clear cell renal cell carcinoma treated with sorafenib or sunitinib

BACKGROUND: We analyzed the expression of heme oxygenase-1 (HO-1) in patients undergoing radical nephrectomy for advanced clear cell renal cell carcinoma (CC-RCC) and evaluated the effects of the targeted therapies treated with sorafenib and sunitinib. METHODS: Expression of HO-1 in cancer tissue from 66 patients was measured by immunohis-tochemical staining. The patients received either oral sorafenib (n=40) or oral sunitinib (n=26) within 4 weeks after nephrectomy and were followed up long term to determine the tumor response and prognosis. RESULTS: Our current study revealed a high HO-1 expression level in 57.6% (38/66) of patients and a low HO-1 expression level in 42.4% (28/66) of patients with CC-RCC. The study also revealed that patients with high HO-1 expression did not have a higher objective response rate (2.6% versus 53.6%, P<0.01), clinical benefit rate (47.4% versus 92.9%, P<0.01), longer progression-free survival (4.4 versus 42 months, P=0.022), or overall survival (χ(2)=4.775, P=0.029) than patients with low HO-1 expression. In the low HO-1 level group, a higher tumor response rate and a longer survival time was achieved in patients who received sorafenib or sunitinib. Multivariate analysis showed that HO-1 expression was an independent prognostic factor for tumor response and overall survival. CONCLUSION: High expression of HO-1 was associated with a lower tumor response rate and a shorter overall survival time when compared with low expression of HO-1. Overall, HO-1 expression might be a useful biomarker for predicting the response to sunitinib and sorafenib for patients with metastatic CC-RCC.