Correlation between Beclin1 Protein Expression and Cervical Cancer Risk: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 WANGYu-juan ¹ , ZHANGJing ¹ , HUOJun-ling ¹ , LVJuan ¹ ,  WANGZan-hong ²

1. Shanxi Medical University, Taiyuan 030001, China;
2. Department of Gynecology, Shanxi Academy of Medical Sciences, Shanxi Da Yi Hospital, Taiyuan 030032, China;

Corresponding?author：

WANGZan-hong, Email: wangzanhong@126.com

Keywords：

Beclin1; Cervical cancer; Systematic review; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20140134

Video：

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Objective To systematically review the correlation between Beclin1 protein expression and cervical cancer as well as its different clinical pathologic features. Methods We electronically searched databases including The Cochrane Library (Issue 1, 2014), PubMed, EMbase, Ovid, CNKI, VIP, CBM and WanFang Data from inception to February 2014, to collect the correlation between Beclin1 protein expression and cervical cancer as well as its different clinical pathologic features. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then meta-analysis was conducted using RevMan 5.2 software. Results A total of 5 case-control studies involving 637 patients were included, of which, 388 cases in the cervical cancer group, 130 cases in the cervical intraepithelial neoplasia (CIN) group, and 119 cases in the normal cervical tissue group. The results of meta-analysis showed that, a) as for Beclin1 expression, significant differences were found in cervical cancer vs. normal cervical tissues (OR=0.07, 95%CI 0.02 to 0.25, P < 0.000 1), cervical cancer vs. CIN (OR=0.37, 95%CI 0.23 to 0.59, P < 0.000 1), CIN vs. normal cervical tissues (OR=0.23, 95%CI 0.06 to 0.88, P=0.03), and cervical cancer tissues with vs. without lymph node metastasis (OR=0.29, 95%CI 0.17 to 0.49, P < 0.000 01). However, no significant difference was found in medium/low differentiation vs. well differentiation (OR=0.50, 95%CI 0.16 to 1.56, P=0.23), tumour diameter no less than vs. less than 4 cm (OR=0.72, 95%CI 0.44 to 1.18, P=0.20), myometrial invasion depth no less than vs. less than 1/2, and FIGO Ⅰ vs. Ⅱ (OR=0.70, 95%CI 0.44 to 1.10, P=0.12). Conclusion Beclin1 protein expression is notably associated to cervical cancer. Due to the limited quantity and quality of the included studies, the above conclusion still needs to be further verified by performing more high quality studies.

Citation： WANGYu-juan, ZHANGJing, HUOJun-ling, LVJuan, WANGZan-hong. Correlation between Beclin1 Protein Expression and Cervical Cancer Risk: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2014, 14(7): 798-805. doi: 10.7507/1672-2531.20140134 Copy

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14.	Shimizu S, Kanaseki T, Mizushima N. Role of Bcl-2 family proteins in a nonapoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol, 2004, 6(12):1221-1228.
15.	Levine B, Yuan J. Autophagy in cell death:an innocent convict. Clin Invest, 2005, 11(5):2679-2688.
16.	Baehrecke EH. Autophagy:dual roles in life and death. Nat Rev Mol Cell Biol, 2005, 6(6):505-510.
17.	Boya P, Gonzalez-Polo RA, Casares N, et al. Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol, 2005, 25(3):1025-1040.
18.	Sun Y, Peng ZL. Autophagy, beclin1, and their relation with oncogenesis. Labmedicine, 2008, 39(5):287-290.
19.	Agarwal A, Balla J, Alam J. Induction of heme oxygenase in toxic renal injury:a protective role in cisplatin nephrotoxicity in the rat. Kidney Int, 1995, 48(4):1298-1307.
20.	程海燕, 張彥娜.自噬相關蛋白Beclin1、LC3在宮頸癌中的表達及臨床意義.中山大學碩士論文, 2009.
21.	Jiang M, Wei Q, Pabla N. Effects of hydroxyl radical scavenging on cisplatin-induced p53 activation, tubular cell apoptosis an nephrotoxicity. Biochem Pharmacol, 2007, 73(9):1499-1510.
22.	Liang XH, Kleeman LK, Jiang HH, et al. Protection against fatal Sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. J Virol, 1998, 72(11):8586-596.
23.	Aim VM, Liang XH, Murty VV, et al. Cloning and cnomic structure of beclin 1, a candidate tumor suppressor ene on chromosome 17q21. Genomics, 1999, 59(1):59-65.
24.	Oberstein A, Jeffrey PD, Shi Y. Crystal structure of the Bcl-XL-Beclin 1 peptide complex:Beclin 1 is a novel BH3-only protein. J Biol Chem, 2007, 282(17):13123-13132.
25.	錢學茜, 萬小云.子宮內膜癌發生過程中自噬活性改變的初步探討.現代婦產科進展, 2008, 17(7):517-519.

1. Parking DM, Bpray F, Ferlay J, et al. Global cancer statistics in 2002. CA Cancer J Clin, 2005, 55(2):74-108.
2. 石峰, 王明榮.細胞自噬及其與腫瘤關系的研究進展.中國細胞生物學學報, 2011, 33(12):1366-1373.
3. 孫陽, 劉佳華.婦科常見腫瘤中細胞自噬現象的研究進展.中華腫瘤防治雜志, 2011, 18(3):233-236.
4. Wang ZH, Xu L, Duan ZL, et al. Beclin 1-mediated macroautophagy involves regulation of caspase-9 expression in cervical cancer HeLa cells. Gynecol Oncol, 2007, 107(1):107-113.
5. Yue Z, Jin S, Yang C, et al. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA, 2003, 100(25):15077-15082.
6. Qu X, Yu J, Bhagat G, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin1 autophagy gene. J Clin Invest, 2003, 112(12):1809-1820.
7. 王贊宏, 彭之蘭.自噬基因Beclinl與宮頸癌相關性的實驗研究.四川大學博士學位論文, 2007.
8. 吳瑞花, 鄭署民. Beclin1、PTEN在子宮頸鱗癌中的表達、相關性及意義.山西醫科大學碩士論文, 2011.
9. 潘小虹, 朱維培.自噬相關基因Beclin1和LC3II在早期宮頸癌組織中的表達及臨床意義.蘭州大學碩士論文, 2012.
10. Cheng HY, Zhang YN, et al. Expression of beclin 1, an autophagy-related protein, in human cervical carcinoma and its clinical significance. Eur J Gynaecol oncol, 2012, 33(1):15-20.
11. 李躍, 王渠源, 張頌婕, 等.自噬基因ARHI與Beclin1在宮頸癌中的表達及意義.中華臨床醫師雜志:電子版, 2013, 7(23):10648-10652.
12. Wells G, Shea B, ÓConnell D, et al. Newcastle-Ottawa Quality Assessment Scale-Case Control Studies. 2012-06-15. Available at:http://www.ohri.ca/programs/clinical-epidemiology/oxford-asp.
13. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J epidemiol, 2010, 25(9):603-605.
14. Shimizu S, Kanaseki T, Mizushima N. Role of Bcl-2 family proteins in a nonapoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol, 2004, 6(12):1221-1228.
15. Levine B, Yuan J. Autophagy in cell death:an innocent convict. Clin Invest, 2005, 11(5):2679-2688.
16. Baehrecke EH. Autophagy:dual roles in life and death. Nat Rev Mol Cell Biol, 2005, 6(6):505-510.
17. Boya P, Gonzalez-Polo RA, Casares N, et al. Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol, 2005, 25(3):1025-1040.
18. Sun Y, Peng ZL. Autophagy, beclin1, and their relation with oncogenesis. Labmedicine, 2008, 39(5):287-290.
19. Agarwal A, Balla J, Alam J. Induction of heme oxygenase in toxic renal injury:a protective role in cisplatin nephrotoxicity in the rat. Kidney Int, 1995, 48(4):1298-1307.
20. 程海燕, 張彥娜.自噬相關蛋白Beclin1、LC3在宮頸癌中的表達及臨床意義.中山大學碩士論文, 2009.
21. Jiang M, Wei Q, Pabla N. Effects of hydroxyl radical scavenging on cisplatin-induced p53 activation, tubular cell apoptosis an nephrotoxicity. Biochem Pharmacol, 2007, 73(9):1499-1510.
22. Liang XH, Kleeman LK, Jiang HH, et al. Protection against fatal Sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. J Virol, 1998, 72(11):8586-596.
23. Aim VM, Liang XH, Murty VV, et al. Cloning and cnomic structure of beclin 1, a candidate tumor suppressor ene on chromosome 17q21. Genomics, 1999, 59(1):59-65.
24. Oberstein A, Jeffrey PD, Shi Y. Crystal structure of the Bcl-XL-Beclin 1 peptide complex:Beclin 1 is a novel BH3-only protein. J Biol Chem, 2007, 282(17):13123-13132.
25. 錢學茜, 萬小云.子宮內膜癌發生過程中自噬活性改變的初步探討.現代婦產科進展, 2008, 17(7):517-519.

Chinese Journal of Evidence-Based Medicine

Correlation between Beclin1 Protein Expression and Cervical Cancer Risk: A Meta-Analysis

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