Correlation between HIF-1α Protein Expression and Renal Cell Cancer Risk: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 TIANYue-jun , GUOQi , CHENZhao-hui , TAOYan , WANGZhi-ping ,  HONGMei

Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Gansu Province for Urological Diseases, Clinical Center of Gansu Province for Nephro-urology, Lanzhou 730030, China;

Corresponding?author：

HONGMei, Email: meihong@bjmu.edu.cn

Keywords：

HIF-1α; Renal cell cancer; Systematic review; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20150173

Video：

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Objective To systematically review the correlation between the expression of hypoxia inducible factor-1α (HIF-1α) protein and different clinical pathological features of renal cell cancer. Methods We electronically searched databases including The Cochrane Library, PubMed, EMbase, CNKI, VIP, CBM and WanFang Data from inception to June 2015 to collect case-control studies investigating the correlation between HIF-1α protein expression and different clinical pathological features of renal cell cancer. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.3 software. Results A total of 8 case-control studies involving 429 cases of renal cell cancer and 130 cases of normal renal tissue were included. The results of meta-analysis showed that:HIF-1α protein expression was higher in the renal cell cancer group than that in the normal renal tissue group (OR=16.76, 95%CI 8.53 to 32.92, P<0.000 01); HIF-1α protein expression was higher in the lymph node metastasis group than that in the non-lymphnode metastasis group (OR=4.33, 95%CI 2.53 to 7.39, P<0.000 01); HIF-1α protein expression was higher in the TNM Ⅲ-IV group than that in the TNM I-Ⅱ group (OR=0.30, 95%CI 0.18 to 0.51, P<0.000 1); HIF-1α protein expression was higher in the Fuhrman pathology classification G3+G4 group than that in the G1+G2 group (OR=0.54, 95%CI 0.29 to 0.98, P=0.04). However, there were no significant differences in HIF-1α protein expression between the age≥50 group and the age <50 group (OR=1.09, 95%CI 0.54 to 2.19, P=0.82), and between the male group and the female group (OR=0.77, 95%CI 0.48 to 1.25, P=0.29). Conclusion HIF-1α protein expression is significantly correlated to the clinical stage and pathological grading of renal cell cancer. It is possibly involved in the initiation and development of renal cell cancer. Due to the limited quantity and quality of included studies, the above conclusion needs to be further verified by more high quality studies.

Citation： TIANYue-jun, GUOQi, CHENZhao-hui, TAOYan, WANGZhi-ping, HONGMei. Correlation between HIF-1α Protein Expression and Renal Cell Cancer Risk: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(9): 1035-1041. doi: 10.7507/1672-2531.20150173 Copy

1.	Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2):87-108.
2.	張歌, 周印, 劉榮波. MRI、MDCT檢測腎癌下腔靜脈癌栓及癌栓侵犯血管壁價值的系統評價. 中國循證醫學雜志, 2013, 13(1):21-25.
3.	Bhatt JR, Finelli A. Landmarks in the diagnosis and treatment of renal cell carcinoma. Nat Rev Urol, 2014, 11(9):517-525.
4.	Brocato J, Chervona Y, Costa M. Molecular responses to hypoxia-inducible factor 1alpha and beyond. Mol Pharmacol, 2014, 85(5):651-657.
5.	Rohwer N, Zasada C, Kempa S, et al. The growing complexity of HIF-1alpha's role in tumorigenesis:DNA repair and beyond. Oncogene, 2013, 32(31):3569-3576.
6.	Medina V, Aparicio G, Santamarina CI, et al. Searching for Hif1-alpha interacting proteins in renal cell carcinoma. Clin Transl Oncol, 2012, 14(9):698-708.
7.	那磊, 吳斌. N F-κB p65和HIF-1α在腎透明細胞癌中的表達及意義. 中國醫科大學學報, 2014, 43 (6):519-522.
8.	嚴新彥, 況應敏. G6PD和HIF-1α在腎透明細胞癌中的表達及其意義. 昆明:昆明醫科大學, 2014.
9.	李培勇, 辛軍, 伍佰聰, 等. HIF-1α、MMP-9、MVD在腎細胞癌中的表達及臨床意義. 重慶醫科大學學報, 2013, 38(2):151-154.
10.	王子夜, 周玉林. PAX2和HIF-1α在腎透明細胞癌中表達相關性的臨床意義初步探討. 安徽:安徽醫科大學, 2013.
11.	舒博, 申鈞, 陳鵬, 等. HIF-1α和P53 蛋白的表達對腎透明細胞癌預后的影響. 現代泌尿外科雜志, 2010, 15(6):435-439.
12.	郝天春, 周林玉, 汪小勇, 等. HIF-1α和CXCR4在腎透明細胞癌中的表達. 安徽醫科大學學報, 2010, 45(2):168-171.
13.	魏澎濤, 喬保平. 腎細胞癌中缺氧誘導因子-1α、2α的表達及與血管生成的關系. 鄭州:鄭州大學, 2007.
14.	李曉峰, 陳仕平. HIF-1α在腎細胞癌中的表達及其與腫瘤血管生成的關系. 福州:福建醫科大學, 2005.
15.	Ke Q, Costa M. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol, 2006, 70(5):1469-1480.
16.	Song X, Liu X, Chi W, et al. Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1alpha gene. Cancer Chemother Pharmacol, 2006, 58 (6):776-784.
17.	Wong CC, Zhang H, Gilkes DM, et al. Inhibitors of hypoxia-inducible factor 1 block breast cancer metastatic niche formation and lung metastasis. J Mol Med (Berl), 2012, 90(7):803-815.
18.	Thapa D, Kang Y, Park PH, et al. Anti-tumor activity of the novel hexahydrocannabinol analog LYR-8 in Human colorectal tumor xenograft is mediated through the inhibition of Akt and hypoxia-inducible factor-1alpha activation. Biol Pharm Bull, 2012, 35(6):924-932.
19.	Kato M, Yamamoto S, Takano M, et al. Aberrant expression of the mammalian target of rapamycin, hypoxia-inducible factor-1alpha, and glucose transporter 1 in the development of ovarian clear-cell adenocarcinoma. Int J Gynecol Pathol, 2012, 31(3):254-263.
20.	Coppin C, Kollmannsberger C, Le L, et al. Targeted therapy for advanced renal cell cancer (RCC):a Cochrane systematic review of published randomised trials. BJU Int, 2011, 108(10):1556-1563.
21.	Oladipupo S, Hu S, Kovalski J, et al. VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting. Proc Natl Acad Sci USA, 2011, 108(32):13264-13269.
22.	Hayes DF. Bevacizumab treatment for solid tumors:boon or bust? JAMA, 2011, 305(5):506-508.
23.	莊乾元, 劉飛, 陳先國, 等. 抗血管生成藥物治療晚期腎癌療效的Meta分析. 中國循證醫學雜志, 2010, 10(6):688-692.
24.	Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma:a double-blind, randomised, placebo-controlled phase Ⅲ trial. Lancet, 2008, 372(9637):449-456.

1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2):87-108.
2. 張歌, 周印, 劉榮波. MRI、MDCT檢測腎癌下腔靜脈癌栓及癌栓侵犯血管壁價值的系統評價. 中國循證醫學雜志, 2013, 13(1):21-25.
3. Bhatt JR, Finelli A. Landmarks in the diagnosis and treatment of renal cell carcinoma. Nat Rev Urol, 2014, 11(9):517-525.
4. Brocato J, Chervona Y, Costa M. Molecular responses to hypoxia-inducible factor 1alpha and beyond. Mol Pharmacol, 2014, 85(5):651-657.
5. Rohwer N, Zasada C, Kempa S, et al. The growing complexity of HIF-1alpha's role in tumorigenesis:DNA repair and beyond. Oncogene, 2013, 32(31):3569-3576.
6. Medina V, Aparicio G, Santamarina CI, et al. Searching for Hif1-alpha interacting proteins in renal cell carcinoma. Clin Transl Oncol, 2012, 14(9):698-708.
7. 那磊, 吳斌. N F-κB p65和HIF-1α在腎透明細胞癌中的表達及意義. 中國醫科大學學報, 2014, 43 (6):519-522.
8. 嚴新彥, 況應敏. G6PD和HIF-1α在腎透明細胞癌中的表達及其意義. 昆明:昆明醫科大學, 2014.
9. 李培勇, 辛軍, 伍佰聰, 等. HIF-1α、MMP-9、MVD在腎細胞癌中的表達及臨床意義. 重慶醫科大學學報, 2013, 38(2):151-154.
10. 王子夜, 周玉林. PAX2和HIF-1α在腎透明細胞癌中表達相關性的臨床意義初步探討. 安徽:安徽醫科大學, 2013.
11. 舒博, 申鈞, 陳鵬, 等. HIF-1α和P53 蛋白的表達對腎透明細胞癌預后的影響. 現代泌尿外科雜志, 2010, 15(6):435-439.
12. 郝天春, 周林玉, 汪小勇, 等. HIF-1α和CXCR4在腎透明細胞癌中的表達. 安徽醫科大學學報, 2010, 45(2):168-171.
13. 魏澎濤, 喬保平. 腎細胞癌中缺氧誘導因子-1α、2α的表達及與血管生成的關系. 鄭州:鄭州大學, 2007.
14. 李曉峰, 陳仕平. HIF-1α在腎細胞癌中的表達及其與腫瘤血管生成的關系. 福州:福建醫科大學, 2005.
15. Ke Q, Costa M. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol, 2006, 70(5):1469-1480.
16. Song X, Liu X, Chi W, et al. Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1alpha gene. Cancer Chemother Pharmacol, 2006, 58 (6):776-784.
17. Wong CC, Zhang H, Gilkes DM, et al. Inhibitors of hypoxia-inducible factor 1 block breast cancer metastatic niche formation and lung metastasis. J Mol Med (Berl), 2012, 90(7):803-815.
18. Thapa D, Kang Y, Park PH, et al. Anti-tumor activity of the novel hexahydrocannabinol analog LYR-8 in Human colorectal tumor xenograft is mediated through the inhibition of Akt and hypoxia-inducible factor-1alpha activation. Biol Pharm Bull, 2012, 35(6):924-932.
19. Kato M, Yamamoto S, Takano M, et al. Aberrant expression of the mammalian target of rapamycin, hypoxia-inducible factor-1alpha, and glucose transporter 1 in the development of ovarian clear-cell adenocarcinoma. Int J Gynecol Pathol, 2012, 31(3):254-263.
20. Coppin C, Kollmannsberger C, Le L, et al. Targeted therapy for advanced renal cell cancer (RCC):a Cochrane systematic review of published randomised trials. BJU Int, 2011, 108(10):1556-1563.
21. Oladipupo S, Hu S, Kovalski J, et al. VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting. Proc Natl Acad Sci USA, 2011, 108(32):13264-13269.
22. Hayes DF. Bevacizumab treatment for solid tumors:boon or bust? JAMA, 2011, 305(5):506-508.
23. 莊乾元, 劉飛, 陳先國, 等. 抗血管生成藥物治療晚期腎癌療效的Meta分析. 中國循證醫學雜志, 2010, 10(6):688-692.
24. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma:a double-blind, randomised, placebo-controlled phase Ⅲ trial. Lancet, 2008, 372(9637):449-456.

Chinese Journal of Evidence-Based Medicine

Correlation between HIF-1α Protein Expression and Renal Cell Cancer Risk: A Meta-analysis

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