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

Zheng WX, Yan F, Xue Q, Wu GJ, Qin WJ, Wang FL, Qin J, Tian CJ, Yuan JL - Onco Targets Ther (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Kaplan–Meier PFS curves of CC-RCC patients with different levels of HO-1 expression.Notes: (A) All patients; (B) sorafenib group; and (C) sunitinib group.Abbreviations: PFS, progression-free survival; CC-RCC, clear cell renal cell carcinoma; HO-1, heme oxygenase-1; n, number of patients.
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f2-ott-8-2081: Kaplan–Meier PFS curves of CC-RCC patients with different levels of HO-1 expression.Notes: (A) All patients; (B) sorafenib group; and (C) sunitinib group.Abbreviations: PFS, progression-free survival; CC-RCC, clear cell renal cell carcinoma; HO-1, heme oxygenase-1; n, number of patients.

Mentions: The prognostic effects in CC-RCC were analyzed by Cox regression analysis. At the time of analysis, the median PFS of the 40 patients treated with sorafenib was 14.63 months (95% CI, 9.23–20.03 months), and the median PFS of the 26 patients treated with sunitinib was not reached. The P-value of the log-rank test was 0.093, which showed that the PFS of the sunitinib group was higher than the sorafenib group. Then, we further evaluated the relationship of HO-1 and PFS. There were 28 (42.4%) and 38 (57.6%) patients classified into the low HO-1 level group and high HO-1 level group, respectively. Median PFS for the low HO-1 group was 42.0 months, whereas those patients with a high HO-1 level had a PFS of 4.4 months (χ2=5.212; P=0.022) (Figure 2A). The present results suggest that CC-RCC patients with a high HO-1 level demonstrated a significantly shorter PFS than those with a low HO-1 level (HR=2.272; 95% CI, 1.102–4.686; P=0.026). We also investigated the potential role of HO-1 in predicting the PFS from sorafenib and sunitinib treatment. The results are shown in Figure 2B and C. In brief, the median PFS of patients who received sorafenib was 16.1 and 4.3 months in the low and high HO-1 level groups (HR=1.629; 95% CI, 0.731–3.626; P=0.233), respectively. The median PFS of patients with a low HO-1 level who received sunitinib was longer than the median PFS in the high HO-1 level group (HR=58.09; 95% CI, 0.261–12939.780; P=0.141; and χ2=7.791; P=0.005, respectively).


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

Zheng WX, Yan F, Xue Q, Wu GJ, Qin WJ, Wang FL, Qin J, Tian CJ, Yuan JL - Onco Targets Ther (2015)

Kaplan–Meier PFS curves of CC-RCC patients with different levels of HO-1 expression.Notes: (A) All patients; (B) sorafenib group; and (C) sunitinib group.Abbreviations: PFS, progression-free survival; CC-RCC, clear cell renal cell carcinoma; HO-1, heme oxygenase-1; n, number of patients.
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Related In: Results  -  Collection

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f2-ott-8-2081: Kaplan–Meier PFS curves of CC-RCC patients with different levels of HO-1 expression.Notes: (A) All patients; (B) sorafenib group; and (C) sunitinib group.Abbreviations: PFS, progression-free survival; CC-RCC, clear cell renal cell carcinoma; HO-1, heme oxygenase-1; n, number of patients.
Mentions: The prognostic effects in CC-RCC were analyzed by Cox regression analysis. At the time of analysis, the median PFS of the 40 patients treated with sorafenib was 14.63 months (95% CI, 9.23–20.03 months), and the median PFS of the 26 patients treated with sunitinib was not reached. The P-value of the log-rank test was 0.093, which showed that the PFS of the sunitinib group was higher than the sorafenib group. Then, we further evaluated the relationship of HO-1 and PFS. There were 28 (42.4%) and 38 (57.6%) patients classified into the low HO-1 level group and high HO-1 level group, respectively. Median PFS for the low HO-1 group was 42.0 months, whereas those patients with a high HO-1 level had a PFS of 4.4 months (χ2=5.212; P=0.022) (Figure 2A). The present results suggest that CC-RCC patients with a high HO-1 level demonstrated a significantly shorter PFS than those with a low HO-1 level (HR=2.272; 95% CI, 1.102–4.686; P=0.026). We also investigated the potential role of HO-1 in predicting the PFS from sorafenib and sunitinib treatment. The results are shown in Figure 2B and C. In brief, the median PFS of patients who received sorafenib was 16.1 and 4.3 months in the low and high HO-1 level groups (HR=1.629; 95% CI, 0.731–3.626; P=0.233), respectively. The median PFS of patients with a low HO-1 level who received sunitinib was longer than the median PFS in the high HO-1 level group (HR=58.09; 95% CI, 0.261–12939.780; P=0.141; and χ2=7.791; P=0.005, respectively).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus