Clinical Significance of CD133 Expression in Gastric Cancer: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 LIUShao-guang ^1,2 , GAOYin-sheng ¹ , HOUYa-bo ¹ ,  GAOPeng ³

1. The First Clinical College of Lanzhou University, Lanzhou 730000, China;
2. Department of Emergency, Gansu Provincial Hospital, Lanzhou 730000, China;
3. The 2^nd Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China;

Corresponding author：

GAOPeng, Email: gaopenglz@yahoo.com

Keywords：

Gastric cancer; CD133; Systematic review; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20140059

Video：

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Objective To systematically review the expression and clinical significance of CD133 in gastric cancer. Methods Searches in the databases such as PubMed, EMbase, Web of Knowledge, The Cochrane Library (Issue 10, 2013), CBM, VIP, CNKI and WanFang Data were performed to collect case-control studies about the association between the CD133 expression and gastric cancer up to October 2013. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies, and then RevMan 5.2 software was used for meta-analysis. Results Nine case-control studies involving 623 patients were included. The results of the meta-analyses showed that, there were significant differences of CD133 expression in the following comparisons:gastric cancer tissues vs. normal esophageal tissues (OR=3.89, 95%CI 1.87 to 8.11, P=0.000 3), lymph node metastasis vs. non-lymph node metastasis (OR=2.75, 95%CI 1.99 to 3.81, P < 0.000 01), clinical stages Ⅲ-Ⅳ vs. clinical stages Ⅰ-Ⅱ (OR=2.83, 95%CI 2.13 to 3.76, P < 0.000 01), as well as distant metastasis vs. non-distant metastasis (OR=2.38, 95%CI 1.47 to 3.85, P=0.000 4). While no significant difference was found between the cell differentiation G1-G2 vs. cell differentiation G3 (OR=1.70, 95%CI 0.90 to 3.21, P=0.10). Conclusion Over-expression of CD133 is associated with lymph node metastasis, distant metastasis and poor TNM stage, which suggests that CD133 may participate in the carcinogenesis of gastric cancer. However, due to the limitations of the included studies, more large-sample high-quality case-control studies are still needed to verify these results.

Citation： LIUShao-guang, GAOYin-sheng, HOUYa-bo, GAOPeng. Clinical Significance of CD133 Expression in Gastric Cancer: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2014, 14(3): 349-354. doi: 10.7507/1672-2531.20140059 Copy

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2.	Han ME, Lee YS, Baek SY, et al. Hedgehog signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2. Int J Mol Sci, 2009, 10(7):3033-3043.
3.	Parker SL, Tong T, Bolden S, et al. Cancer statistics, 1997. CA Cancer J Clin, 1997, 47(1):5-27.
4.	秦薇, 张晓伟, 章莉, 等. Oct-4在胃癌组织中的表达及临床意义.上海交通大学学报(医学版), 2009, 29(6):733-736.
5.	Soltysova A, Altanerova V, Altaner C. Cancer stem cells. Neoplasma, 2005, 52(6):435-440.
6.	Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature, 2001, 414(6859):105-111.
7.	Chen S, Hou JH, Feng XY, et al. Clinicopathologic significance of putative stem cell marker, CD44 and CD133, in human gastric carcinoma. J Surg Oncol, 2013, 107(8):799-806.
8.	Hashimoto K, Aoyagi K, Isobe T, et al. Expression of CD133 in the cytoplasm is associated with cancer progression and poor prognosis in gastric cancer. Gastric Cancer, 2014, 17(1):97-106.
9.	Ishigami S, Ueno S, Arigami T, et al. Prognostic impact of CD133 expression in gastric carcinoma. Anticancer Res, 2010, 30(6):2453-2457.
10.	陆瑞祺, 吴巨钢, 周国才, 等.胃癌中CXCR4和CD133的表达及其对淋巴转移的影响.中国普通外科杂志, 2012, 21(4):415-420.
11.	Wakamatsu Y, Sakamoto N, Oo HZ, et al. Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathol Int, 2012, 62(2):112-119.
12.	Wang T, Ong CW, Shi J, et al. Sequential expression of putative stem cell markers in gastric carcinogenesis. Br J Cancer, 2011, 105(5):658-665.
13.	薛英明, 孙培春, 吴刚, 等. CD133在胃癌组织中的表达及临床意义.中华实用诊断与治疗杂志, 2011, 25(4):355-357.
14.	张鹏, 吴巨钢, 俞继卫, 等.胃癌组织中CD133蛋白表达及其临床意义.中国普外基础与临床杂志, 2011, 18(3):281-285.
15.	Zhao P, Li Y, Lu Y. Aberrant expression of CD133 protein correlates with Ki-67 expression and is a prognostic marker in gastric adenocarcinoma. BMC Cancer, 2010, 10:218.
16.	Wells GA, Shea B, O'connell D, et al. The Newcastle-Ottawa Scale(NOS) for assessing the quality of nonrandomised studies in metaanalyses. 3rd Symposium on Systematic Reviews:Beyond the Basics. 2000.
17.	Yu JW, Zhang P, Wu JG, et al. Expressions and clinical significances of CD133 protein and CD133 mRNA in primary lesion of gastric adenocacinoma. J Exp Clin Cancer Res, 2010, 29:141.
18.	Corbeil D, Roper K, Fargeas CA, et al. Prominin:a story of cholesterol, plasma membrane protrusions and human pathology. Traffic, 2001, 2(2):82-91.
19.	Smith LM, Nesterova A, Ryan MC, et al. CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br J Cancer, 2008, 99(1):100-109.
20.	陆瑞祺, 吴巨钢, 周国才, 等.胃癌CD133阳性细胞的纯化及其生物学特性研究.中国普外基础与临床杂志, 2011, 18(12):1265-1270.
21.	Chen S, Song X, Chen Z, et al. CD133 expression and the prognosis of colorectal cancer:a systematic review and meta-analysis. PLoS One, 2013, 8(2):e56380.
22.	苟云久, 何晓东, 谢定雄, 等.非小细胞肺癌组织中CD133表达及临床意义的Meta分析.中国组织工程研究, 2013, 17(23):4292-4298.
23.	Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature, 2004, 432(7015):396-401.
24.	Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res, 2005, 65(23):10946-10951.
25.	Wen L, Chen XZ, Yang K, et al. Prognostic value of cancer stem cell marker CD133 expression in gastric cancer:a systematic review. PLoS One, 2013, 8(3):e59154.
26.	Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res, 2003, 63(18):5821-5828.
27.	Beier D, Hau P, Proescholdt M, et al. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res, 2007, 67(9):4010-4015.

1. Brenner H, Rothenbacher D, Arndt V. Epidemiology of stomach cancer. Methods Mol Biol, 2009, 472(3):467-477.
2. Han ME, Lee YS, Baek SY, et al. Hedgehog signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2. Int J Mol Sci, 2009, 10(7):3033-3043.
3. Parker SL, Tong T, Bolden S, et al. Cancer statistics, 1997. CA Cancer J Clin, 1997, 47(1):5-27.
4. 秦薇, 张晓伟, 章莉, 等. Oct-4在胃癌组织中的表达及临床意义.上海交通大学学报(医学版), 2009, 29(6):733-736.
5. Soltysova A, Altanerova V, Altaner C. Cancer stem cells. Neoplasma, 2005, 52(6):435-440.
6. Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature, 2001, 414(6859):105-111.
7. Chen S, Hou JH, Feng XY, et al. Clinicopathologic significance of putative stem cell marker, CD44 and CD133, in human gastric carcinoma. J Surg Oncol, 2013, 107(8):799-806.
8. Hashimoto K, Aoyagi K, Isobe T, et al. Expression of CD133 in the cytoplasm is associated with cancer progression and poor prognosis in gastric cancer. Gastric Cancer, 2014, 17(1):97-106.
9. Ishigami S, Ueno S, Arigami T, et al. Prognostic impact of CD133 expression in gastric carcinoma. Anticancer Res, 2010, 30(6):2453-2457.
10. 陆瑞祺, 吴巨钢, 周国才, 等.胃癌中CXCR4和CD133的表达及其对淋巴转移的影响.中国普通外科杂志, 2012, 21(4):415-420.
11. Wakamatsu Y, Sakamoto N, Oo HZ, et al. Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathol Int, 2012, 62(2):112-119.
12. Wang T, Ong CW, Shi J, et al. Sequential expression of putative stem cell markers in gastric carcinogenesis. Br J Cancer, 2011, 105(5):658-665.
13. 薛英明, 孙培春, 吴刚, 等. CD133在胃癌组织中的表达及临床意义.中华实用诊断与治疗杂志, 2011, 25(4):355-357.
14. 张鹏, 吴巨钢, 俞继卫, 等.胃癌组织中CD133蛋白表达及其临床意义.中国普外基础与临床杂志, 2011, 18(3):281-285.
15. Zhao P, Li Y, Lu Y. Aberrant expression of CD133 protein correlates with Ki-67 expression and is a prognostic marker in gastric adenocarcinoma. BMC Cancer, 2010, 10:218.
16. Wells GA, Shea B, O'connell D, et al. The Newcastle-Ottawa Scale(NOS) for assessing the quality of nonrandomised studies in metaanalyses. 3rd Symposium on Systematic Reviews:Beyond the Basics. 2000.
17. Yu JW, Zhang P, Wu JG, et al. Expressions and clinical significances of CD133 protein and CD133 mRNA in primary lesion of gastric adenocacinoma. J Exp Clin Cancer Res, 2010, 29:141.
18. Corbeil D, Roper K, Fargeas CA, et al. Prominin:a story of cholesterol, plasma membrane protrusions and human pathology. Traffic, 2001, 2(2):82-91.
19. Smith LM, Nesterova A, Ryan MC, et al. CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br J Cancer, 2008, 99(1):100-109.
20. 陆瑞祺, 吴巨钢, 周国才, 等.胃癌CD133阳性细胞的纯化及其生物学特性研究.中国普外基础与临床杂志, 2011, 18(12):1265-1270.
21. Chen S, Song X, Chen Z, et al. CD133 expression and the prognosis of colorectal cancer:a systematic review and meta-analysis. PLoS One, 2013, 8(2):e56380.
22. 苟云久, 何晓东, 谢定雄, 等.非小细胞肺癌组织中CD133表达及临床意义的Meta分析.中国组织工程研究, 2013, 17(23):4292-4298.
23. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature, 2004, 432(7015):396-401.
24. Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res, 2005, 65(23):10946-10951.
25. Wen L, Chen XZ, Yang K, et al. Prognostic value of cancer stem cell marker CD133 expression in gastric cancer:a systematic review. PLoS One, 2013, 8(3):e59154.
26. Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res, 2003, 63(18):5821-5828.
27. Beier D, Hau P, Proescholdt M, et al. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res, 2007, 67(9):4010-4015.

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