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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 OS curves of CC-RCC patients with different levels of HO-1 expression.Notes: (A) All patients; (B) sorafenib group; (C) sunitinib group.Abbreviations: OS, overall survival; CC-RCC, clear cell renal cell carcinoma; HO-1, heme oxygenase-1; n, number of patients.
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f3-ott-8-2081: Kaplan–Meier OS curves of CC-RCC patients with different levels of HO-1 expression.Notes: (A) All patients; (B) sorafenib group; (C) sunitinib group.Abbreviations: OS, overall survival; CC-RCC, clear cell renal cell carcinoma; HO-1, heme oxygenase-1; n, number of patients.

Mentions: At the time of data analysis, the median OS had not been reached in the sunitinib group, and the median OS was 48.97 months among patients treated with sorafenib; the difference was statistically significant (log-rank test, χ2=4.467; P=0.035). Then, we further evaluated the relationship of HO-1 and OS. The median OS in patients with a high expression of HO-1 was significantly shorter than in patients with a low expression of HO-1 (HR=3.425; 95% CI, 1.069–10.973 P=0.038; and χ2=4.775; P=0.029, respectively) (Figure 3A). The same results were achieved in the patients who were treated with sorafenib (HR=3.826, 95% CI, 1.148–12.749; P=0.029; and χ2=5.395, P=0.020) or sunitinib (HR=41.165, 95% CI, 0.000–6937271.379; P=0.545; and χ2=1.122; P=0.290, respectively), that is to say, in the high HO-1 group, regardless of the treatment provided, the patients had a shorter OS compared with the low HO-1 group (Figure 3B and C).


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 OS curves of CC-RCC patients with different levels of HO-1 expression.Notes: (A) All patients; (B) sorafenib group; (C) sunitinib group.Abbreviations: OS, overall 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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getmorefigures.php?uid=PMC4539079&req=5

f3-ott-8-2081: Kaplan–Meier OS curves of CC-RCC patients with different levels of HO-1 expression.Notes: (A) All patients; (B) sorafenib group; (C) sunitinib group.Abbreviations: OS, overall survival; CC-RCC, clear cell renal cell carcinoma; HO-1, heme oxygenase-1; n, number of patients.
Mentions: At the time of data analysis, the median OS had not been reached in the sunitinib group, and the median OS was 48.97 months among patients treated with sorafenib; the difference was statistically significant (log-rank test, χ2=4.467; P=0.035). Then, we further evaluated the relationship of HO-1 and OS. The median OS in patients with a high expression of HO-1 was significantly shorter than in patients with a low expression of HO-1 (HR=3.425; 95% CI, 1.069–10.973 P=0.038; and χ2=4.775; P=0.029, respectively) (Figure 3A). The same results were achieved in the patients who were treated with sorafenib (HR=3.826, 95% CI, 1.148–12.749; P=0.029; and χ2=5.395, P=0.020) or sunitinib (HR=41.165, 95% CI, 0.000–6937271.379; P=0.545; and χ2=1.122; P=0.290, respectively), that is to say, in the high HO-1 group, regardless of the treatment provided, the patients had a shorter OS compared with the low HO-1 group (Figure 3B and C).

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