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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

Representative images of immunoreactivity for HO-1 in tumor tissues.Notes: (A) Positive expression; (B) negative expression (magnification, 400×).Abbreviation: HO-1, heme oxygenase-1.
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f1-ott-8-2081: Representative images of immunoreactivity for HO-1 in tumor tissues.Notes: (A) Positive expression; (B) negative expression (magnification, 400×).Abbreviation: HO-1, heme oxygenase-1.

Mentions: HO-1 was mainly expressed in the cytoplasm of the tumor cells (Figure 1). The optimal value of the average optical density was evaluated by the ROC curve and Youden index to measure the expression level of HO-1. The sensitivity and specificity of this cutoff value in predicting tumor CR/PR and SD/PD was 74.0% and 93.7%, respectively. We then defined high HO-1 expression as a value of >0.087, and low HO-1 expression as a value of <0.087. In our results, 57.6% (38/66) of CC-RCC patients had high HO-1 expression, and 42.4% (28/66) patients had low expression.


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)

Representative images of immunoreactivity for HO-1 in tumor tissues.Notes: (A) Positive expression; (B) negative expression (magnification, 400×).Abbreviation: HO-1, heme oxygenase-1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539079&req=5

f1-ott-8-2081: Representative images of immunoreactivity for HO-1 in tumor tissues.Notes: (A) Positive expression; (B) negative expression (magnification, 400×).Abbreviation: HO-1, heme oxygenase-1.
Mentions: HO-1 was mainly expressed in the cytoplasm of the tumor cells (Figure 1). The optimal value of the average optical density was evaluated by the ROC curve and Youden index to measure the expression level of HO-1. The sensitivity and specificity of this cutoff value in predicting tumor CR/PR and SD/PD was 74.0% and 93.7%, respectively. We then defined high HO-1 expression as a value of >0.087, and low HO-1 expression as a value of <0.087. In our results, 57.6% (38/66) of CC-RCC patients had high HO-1 expression, and 42.4% (28/66) patients had low expression.

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