Significance of autophagy-related protein Beclin-1 expression in patients with gastric cancer: a meta-analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WU Bingjie ¹ ,  LI Xiaoli ²

1. Shanxi Medical University, Taiyuan 030000, P. R. China;
2. Department of Gastroenterology, The First Hospital of Shanxi Medical University, Taiyuan 030000, P. R. China;

Corresponding?author：

LI Xiaoli, Email: lxl329329@163.com

Keywords：

autophagy; Beclin-1; gastric cancer; meta-analysis

DOI：

10.7507/1007-9424.201811052

Video：

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Objective To systematically evaluate relationship between expression of autophagy-related protein Beclin-1 in gastric cancer and its clinicopathologic features and its clinical significances.Methods The researches on the expression and significance of Beclin-1 protein in the gastric tumor tissues published from the database establishment to June 1, 2018 in the Cochrane Library, Springer Link, Web of Science, Embase, PubMed, CNKI, Wanfang, VIP, and other databases were searched. Two researchers independently screened and evaluated the literatures, extracted the relevant data, and conducted the meta-analysis using the Review Manager 5.3 and Stata 15.0 software.Results Finally, 10 articles were included, and there were 1 402 patients with gastric cancer. The meta-analysis showed that the positive rate of Beclin1 protein expression in the gastric cancer tissues was significantly lower than that in the non-gastric cancer tissues [OR=0.30, 95% CI (0.13, 0.72), P=0.007], which in the patients with TNM stage Ⅲ/Ⅳ and distant metastatic gastric cancer were significantly lower than those in the patients with stage Ⅰ/Ⅱ [OR=1.82, 95% CI (1.03, 3.20), P=0.04] and without distant metastasis [OR=0.36, 95% CI (0.20, 0.63), P=0.000 4], which were not associated with the gender, age, tumor size, lymph node metastasis, serosa invasion, and tumor differentiation degree of gastric cancer patients (P>0.05). For the studies of existed heterogeneity, further the subgroup analysis showed that the positive expression rate of Beclin-1 protein in the gastric cancer tissues was significantly lower than that in the non-gastric cancer tissues [OR=0.19, 95% CI (0.13, 0.29), P<0.000 01], which in the patients with lymph node metastasis, invasion of serosa, and poorly differentiated gastric cancer were significantly lower than those in the non-lymph node metastasis [OR=0.35, 95% CI (0.22, 0.57), P<0.000 1], non-invasion of serosa [OR=0.56, 95% CI (0.33, 0.94), P=0.03], and moderately/highly differentiated gastric cancer tissues [OR=0.29, 95% CI (0.20, 0.43), P<0.000 01].Conclusions Low expression of Beclin-1 in gastric cancer tissues is related to stage and distant metastasis of gastric cancer. It is suggested that it might not only be an important cause of gastric cancer, but also play a regulatory role in progress of gastric cancer.

Citation： WU Bingjie, LI Xiaoli. Significance of autophagy-related protein Beclin-1 expression in patients with gastric cancer: a meta-analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(3): 315-325. doi: 10.7507/1007-9424.201811052 Copy

1.	左婷婷, 鄭榮壽, 曾紅梅, 等. 中國胃癌流行病學現狀. 中國腫瘤臨床, 2017, 44(1): 52-58.
2.	Marinkovi? M, ?prung M, Buljuba?i? M, et al. Autophagy modulation in cancer: current knowledge on action and therapy. Oxid Med Cell Longev, 2018, 2018: 8023821.
3.	余招焱, 王潤華, 張忠民, 等. 自噬及其在胃癌中的研究進展. 中國普外基礎與臨床雜志, 2015, 22(1): 121-125.
4.	Sipos F, Székely H, Kis ID, et al. Relation of the IGF/IGF1R system to autophagy in colitis and colorectal cancer. World J Gastroenterol, 2017, 23(46): 8109-8119.
5.	Khambu B, Huda N, Chen X, et al. HMGB1 promotes ductular reaction and tumorigenesis in autophagy-deficient livers. J Clin Invest, 2018, 128(6): 2419-2435.
6.	Grootaert MOJ, Roth L, Schrijvers DM, et al. Defective autophagy in atherosclerosis: To die or to senesce? Oxid Med Cell Longev, 2018, 2018: 7687083.
7.	Fang C, Gu L, Smerin D, et al. The interrelation between reactive oxygen species and autophagy in neurological disorders. Oxid Med Cell Longev, 2017, 2017: 8495160.
8.	崔丹蕊, 劉波, 劉偉. 細胞自噬與腫瘤發生關系的研究進展. 中國科學: 生命科學, 2015, 45(6): 593-603.
9.	杜云廣, 王書華. 細胞自噬及其與腫瘤發生關系的研究進展. 河北北方學院學報(自然科學版), 2018, 34(2): 49-55.
10.	Chen YB, Hou JH, Feng XY, et al. Decreased expression of Beclin 1 correlates with a metastatic phenotypic feature and adverse prognosis of gastric carcinomas. J Surg Oncol, 2012, 105(6): 542-547.
11.	Zhou WH, Tang F, Xu J, et al. Low expression of Beclin 1, associated with high Bcl-xL, predicts a malignant phenotype and poor prognosis of gastric cancer. Autophagy, 2012, 8(3): 389-400.
12.	Yu M, Gou WF, Zhao S, et al. Beclin 1 expression is an independent prognostic factor for gastric carcinomas. Tumour Biol, 2013, 34(2): 1071-1083.
13.	Wang Y, Xie J, Wang H, et al. Beclin-1 suppresses gastric cancer progression by promoting apoptosis and reducing cell migration. Oncol Lett, 2017, 14(6): 6857-6862.
14.	Huang X, Wang C, Sun J, et al. Clinical value of CagA, c-Met, PI3K and Beclin-1 expressed in gastric cancer and their association with prognosis. Oncol Lett, 2018, 15(1): 947-955.
15.	羅小月, 嚴倩, 彭美玲, 等. Beclin1 和 LC3 在胃癌組織中的表達水平和臨床意義. 湖南師范大學學報(醫學版), 2016, 13(4): 4-7.
16.	李良慶, 潘敦, 林振孟. 自噬相關基因 Beclin1 和微管相關蛋白輕鏈 3 在胃癌組織中的表達及臨床意義. 中華實驗外科雜志, 2014, 31(3): 508-510.
17.	袁文敏, 林梅. 胃癌組織 Beclin-1 與 Bcl-2 的表達及其意義. 青島大學, 2016.
18.	黃俊玲, 鐘騰猛, 黃贊松, 等. 自噬因子 Beclin 1 和 LC3 表達與胃癌臨床病理特征的相關性研究. 實用癌癥雜志, 2016, 31(4): 530-532.
19.	宋華勇, 馬磊. 自噬相關基因 Beclin 1 和微管相關蛋白輕鏈 3 在胃癌組織中的表達及臨床意義. 泰山醫學院學報, 2017, 38(7): 731-733.
20.	Yin Q, Feng W, Shen X, et al. Regulatory effects of lncRNAs and miRNAs on autophagy in malignant tumorigenesis. Biosci Rep, 2018, 38(5): pii: BSR20180516.
21.	Ahn CH, Jeong EG, Lee JW, et al. Expression of beclin-1, an autophagy-related protein, in gastric and colorectal cancers. APMIS, 2007, 115(12): 1344-1349.
22.	Xia P, Wang JJ, Zhao BB, et al. The role of beclin-1 expression in patients with gastric cancer: a meta-analysis. Tumour Biol, 2013, 34(6): 3303-3307.
23.	Liang C, Li W, Ge H, et al. Role of Beclin1 expression in patients with hepatocellular carcinoma: a meta-analysis. Onco Targets Ther, 2018, 11: 2387-2397.
24.	高金雪, 吳清明, 劉丹. 大腸癌組織自噬相關蛋白 Beclin1 表達意義 Meta 分析. 中華腫瘤防治雜志, 2017, 24(4): 273-277.
25.	霍小蕾, 王金勝, 張毅強, 等. FoxO1 及自噬相關基因 Beclin1 和 MAPLC3 在胃癌組織的表達及意義. 西安交通大學學報(醫學版), 2017, 38(5): 773-776.
26.	鄭華川, 申道福, 楊雪峰, 等. Beclin 1 表達在胃癌發生和演進中的臨床病理意義及作用機制. 中國醫科大學學報, 2015, 44(12): 1061-1065.
27.	林哲洙, 張紅, 張磊, 等. Beclin1 基因在胃癌發生和演進中的分子作用機制. 中國老年學雜志, 2015, (16): 4477-4479.
28.	Qin W, Li C, Zheng W, et al. Inhibition of autophagy promotes metastasis and glycolysis by inducing ROS in gastric cancer cells. Oncotarget, 2015, 6(37): 39839-39854.

1. 左婷婷, 鄭榮壽, 曾紅梅, 等. 中國胃癌流行病學現狀. 中國腫瘤臨床, 2017, 44(1): 52-58.
2. Marinkovi? M, ?prung M, Buljuba?i? M, et al. Autophagy modulation in cancer: current knowledge on action and therapy. Oxid Med Cell Longev, 2018, 2018: 8023821.
3. 余招焱, 王潤華, 張忠民, 等. 自噬及其在胃癌中的研究進展. 中國普外基礎與臨床雜志, 2015, 22(1): 121-125.
4. Sipos F, Székely H, Kis ID, et al. Relation of the IGF/IGF1R system to autophagy in colitis and colorectal cancer. World J Gastroenterol, 2017, 23(46): 8109-8119.
5. Khambu B, Huda N, Chen X, et al. HMGB1 promotes ductular reaction and tumorigenesis in autophagy-deficient livers. J Clin Invest, 2018, 128(6): 2419-2435.
6. Grootaert MOJ, Roth L, Schrijvers DM, et al. Defective autophagy in atherosclerosis: To die or to senesce? Oxid Med Cell Longev, 2018, 2018: 7687083.
7. Fang C, Gu L, Smerin D, et al. The interrelation between reactive oxygen species and autophagy in neurological disorders. Oxid Med Cell Longev, 2017, 2017: 8495160.
8. 崔丹蕊, 劉波, 劉偉. 細胞自噬與腫瘤發生關系的研究進展. 中國科學: 生命科學, 2015, 45(6): 593-603.
9. 杜云廣, 王書華. 細胞自噬及其與腫瘤發生關系的研究進展. 河北北方學院學報(自然科學版), 2018, 34(2): 49-55.
10. Chen YB, Hou JH, Feng XY, et al. Decreased expression of Beclin 1 correlates with a metastatic phenotypic feature and adverse prognosis of gastric carcinomas. J Surg Oncol, 2012, 105(6): 542-547.
11. Zhou WH, Tang F, Xu J, et al. Low expression of Beclin 1, associated with high Bcl-xL, predicts a malignant phenotype and poor prognosis of gastric cancer. Autophagy, 2012, 8(3): 389-400.
12. Yu M, Gou WF, Zhao S, et al. Beclin 1 expression is an independent prognostic factor for gastric carcinomas. Tumour Biol, 2013, 34(2): 1071-1083.
13. Wang Y, Xie J, Wang H, et al. Beclin-1 suppresses gastric cancer progression by promoting apoptosis and reducing cell migration. Oncol Lett, 2017, 14(6): 6857-6862.
14. Huang X, Wang C, Sun J, et al. Clinical value of CagA, c-Met, PI3K and Beclin-1 expressed in gastric cancer and their association with prognosis. Oncol Lett, 2018, 15(1): 947-955.
15. 羅小月, 嚴倩, 彭美玲, 等. Beclin1 和 LC3 在胃癌組織中的表達水平和臨床意義. 湖南師范大學學報(醫學版), 2016, 13(4): 4-7.
16. 李良慶, 潘敦, 林振孟. 自噬相關基因 Beclin1 和微管相關蛋白輕鏈 3 在胃癌組織中的表達及臨床意義. 中華實驗外科雜志, 2014, 31(3): 508-510.
17. 袁文敏, 林梅. 胃癌組織 Beclin-1 與 Bcl-2 的表達及其意義. 青島大學, 2016.
18. 黃俊玲, 鐘騰猛, 黃贊松, 等. 自噬因子 Beclin 1 和 LC3 表達與胃癌臨床病理特征的相關性研究. 實用癌癥雜志, 2016, 31(4): 530-532.
19. 宋華勇, 馬磊. 自噬相關基因 Beclin 1 和微管相關蛋白輕鏈 3 在胃癌組織中的表達及臨床意義. 泰山醫學院學報, 2017, 38(7): 731-733.
20. Yin Q, Feng W, Shen X, et al. Regulatory effects of lncRNAs and miRNAs on autophagy in malignant tumorigenesis. Biosci Rep, 2018, 38(5): pii: BSR20180516.
21. Ahn CH, Jeong EG, Lee JW, et al. Expression of beclin-1, an autophagy-related protein, in gastric and colorectal cancers. APMIS, 2007, 115(12): 1344-1349.
22. Xia P, Wang JJ, Zhao BB, et al. The role of beclin-1 expression in patients with gastric cancer: a meta-analysis. Tumour Biol, 2013, 34(6): 3303-3307.
23. Liang C, Li W, Ge H, et al. Role of Beclin1 expression in patients with hepatocellular carcinoma: a meta-analysis. Onco Targets Ther, 2018, 11: 2387-2397.
24. 高金雪, 吳清明, 劉丹. 大腸癌組織自噬相關蛋白 Beclin1 表達意義 Meta 分析. 中華腫瘤防治雜志, 2017, 24(4): 273-277.
25. 霍小蕾, 王金勝, 張毅強, 等. FoxO1 及自噬相關基因 Beclin1 和 MAPLC3 在胃癌組織的表達及意義. 西安交通大學學報(醫學版), 2017, 38(5): 773-776.
26. 鄭華川, 申道福, 楊雪峰, 等. Beclin 1 表達在胃癌發生和演進中的臨床病理意義及作用機制. 中國醫科大學學報, 2015, 44(12): 1061-1065.
27. 林哲洙, 張紅, 張磊, 等. Beclin1 基因在胃癌發生和演進中的分子作用機制. 中國老年學雜志, 2015, (16): 4477-4479.
28. Qin W, Li C, Zheng W, et al. Inhibition of autophagy promotes metastasis and glycolysis by inducing ROS in gastric cancer cells. Oncotarget, 2015, 6(37): 39839-39854.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Significance of autophagy-related protein Beclin-1 expression in patients with gastric cancer: a meta-analysis

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