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.	张歌, 周印, 刘荣波. MRI、MDCT检测肾癌下腔静脉癌栓及癌栓侵犯血管壁价值的系统评价. 中国循证医学杂志, 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, 吴斌. N F-κB p65和HIF-1α在肾透明细胞癌中的表达及意义. 中国医科大学学报, 2014, 43 (6):519-522.
8.	严新彦, 况应敏. G6PD和HIF-1α在肾透明细胞癌中的表达及其意义. 昆明:昆明医科大学, 2014.
9.	李培勇, 辛军, 伍佰聪, 等. HIF-1α、MMP-9、MVD在肾细胞癌中的表达及临床意义. 重庆医科大学学报, 2013, 38(2):151-154.
10.	王子夜, 周玉林. PAX2和HIF-1α在肾透明细胞癌中表达相关性的临床意义初步探讨. 安徽:安徽医科大学, 2013.
11.	舒博, 申钧, 陈鹏, 等. HIF-1α和P53 蛋白的表达对肾透明细胞癌预后的影响. 现代泌尿外科杂志, 2010, 15(6):435-439.
12.	郝天春, 周林玉, 汪小勇, 等. HIF-1α和CXCR4在肾透明细胞癌中的表达. 安徽医科大学学报, 2010, 45(2):168-171.
13.	魏澎涛, 乔保平. 肾细胞癌中缺氧诱导因子-1α、2α的表达及与血管生成的关系. 郑州:郑州大学, 2007.
14.	李晓峰, 陈仕平. HIF-1α在肾细胞癌中的表达及其与肿瘤血管生成的关系. 福州:福建医科大学, 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.	庄乾元, 刘飞, 陈先国, 等. 抗血管生成药物治疗晚期肾癌疗效的Meta分析. 中国循证医学杂志, 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. 张歌, 周印, 刘荣波. MRI、MDCT检测肾癌下腔静脉癌栓及癌栓侵犯血管壁价值的系统评价. 中国循证医学杂志, 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, 吴斌. N F-κB p65和HIF-1α在肾透明细胞癌中的表达及意义. 中国医科大学学报, 2014, 43 (6):519-522.
8. 严新彦, 况应敏. G6PD和HIF-1α在肾透明细胞癌中的表达及其意义. 昆明:昆明医科大学, 2014.
9. 李培勇, 辛军, 伍佰聪, 等. HIF-1α、MMP-9、MVD在肾细胞癌中的表达及临床意义. 重庆医科大学学报, 2013, 38(2):151-154.
10. 王子夜, 周玉林. PAX2和HIF-1α在肾透明细胞癌中表达相关性的临床意义初步探讨. 安徽:安徽医科大学, 2013.
11. 舒博, 申钧, 陈鹏, 等. HIF-1α和P53 蛋白的表达对肾透明细胞癌预后的影响. 现代泌尿外科杂志, 2010, 15(6):435-439.
12. 郝天春, 周林玉, 汪小勇, 等. HIF-1α和CXCR4在肾透明细胞癌中的表达. 安徽医科大学学报, 2010, 45(2):168-171.
13. 魏澎涛, 乔保平. 肾细胞癌中缺氧诱导因子-1α、2α的表达及与血管生成的关系. 郑州:郑州大学, 2007.
14. 李晓峰, 陈仕平. HIF-1α在肾细胞癌中的表达及其与肿瘤血管生成的关系. 福州:福建医科大学, 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. 庄乾元, 刘飞, 陈先国, 等. 抗血管生成药物治疗晚期肾癌疗效的Meta分析. 中国循证医学杂志, 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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