Expressions of CD133 and CD44 Protein in Primary Lesion of Gastric Cancer and Its Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIWei ¹ , JIANGBo-jian ¹ ,  YUJi-wei ^1,2

1. 1st Department of General Surgery, The Third People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China;
2. Department of Postgraduate of Bengbu Medical College, Bengbu 233000, Anhui Province, China;

Corresponding author：

YUJi-wei, Email: jiweiyu919@hotmail.com

Keywords：

Gastric cancer; CD133 protein; CD44 protein; Lymph node metastasis; Clinicopathologic feature; Prognosis

DOI：

10.7507/1007-9424.20140005

Video：

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Objective To investigate the expressions of CD133 and CD44 protein in primary lesions of gastric cancer and its clinical significance. Methods The expressions of CD44 and CD133 protein in gastric cancer tissues of 100 patients with gastric cancer were detected by immunohistocheimcal stainings.The relation between the expressions of CD44 and CD133 protein and the clinicopathologic characters were analyzed. Results Both CD44 and CD133 protein were expressed on the cell membranes.No correlation were found between CD44/CD133 and the clinicopathologic parameters include gender and age (P > 0.05), but the positive expression rate of CD44/CD133 with diameter>5 cm was significantly higher than that tumor with diameter≤5 cm (CD44 P=0.150;CD133 P=0.056), and correlated with the tissue differentiation (CD44 P=0.008;CD133 P=0.007), vascular invasion (CD44 P=0.043;CD133 P=0.023), lymphatic vessel invasion (CD44 P=0.020;CD133 P=0.044), lymph nodes metastasis (CD44 P=0.002;CD133 P=0.004), inva-sion depth of tumor (CD44 P=0.006;CD133 P=0.021), and pTNM stage (CD44 P=0.034;CD133 P=0.001).No correlation were found between the co-expression of CD44 and CD133 protein and the clinicopathologic parameters include gender, age, tissue differentiation, and vascular invasion (P > 0.05), but the positive co-expression rate of CD44 and CD133 with diameter>5 cm was significantly higher than that tumor with diameter≤5 cm (P=0.010), and correlated with lymphatic vessel invasion (P=0.003), lymph nodes metastasis (P=0.045), invasion depth of tumor (P=0.041), and pTNM stage (P=0.049).The Spearman rank correlation analysis showed that there was positive correlation between the expressions of CD44 and CD133 protein (r=0.207, P=0.039).Univariate analysis showed that lymph nodes metastasis (P < 0.001), pTNM stages (P=0.013), CD44 protein expression (P=0.005), CD133 protein expression (P=0.002), and co-expression of CD44 and CD133 protein (P < 0.001) were significantly correlated with 3-year survival rate of pati-ents with gastric cancer respectively.Logistic regression analysis revealed that lymph node metastasis (P=0.038) was independent risk factor for co-expression of CD44 and CD133 protein.Multivariate analysis with the Cox regression models showed that co-expression of CD44 and CD133 protein (P=0.003) and lymph node metastasis (P=0.006) were significantly associated with poor prognosis. Conclusions CD44 and CD133 protein may be considered as robust cancer stem cell markers in gastric cancer.The co-expression of CD44 and CD133 protein is the independent prognosis factor for gastric cancer and strongly associated with poor prognosis when they are expressed more high.

Citation： LIWei, JIANGBo-jian, YUJi-wei. Expressions of CD133 and CD44 Protein in Primary Lesion of Gastric Cancer and Its Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(1): 21-28. doi: 10.7507/1007-9424.20140005 Copy

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16.	Huang X, Sheng Y, Guan M.Co-expression of stem cell genes CD133 and CD44 in colorectal cancers with early liver metastasis[J].Surg Oncol, 2012, 21(2):103-107.
17.	Ponta H, Sherman L, Herrlich PA.CD44:from adhesion molecules to signalling regulators[J].Nat Rev Mol Cell Biol, 2003, 4(1):33-45.
18.	Ishimoto T, Oshima H, Oshima M, et al.CD44⁺ slow-cycling tumor cell expansion is triggered by cooperative actions of Wnt and prostaglandin E2 in gastric tumorigenesis[J].Cancer Sci, 2010, 101(3):673-678.
19.	姜海广, 陆瑞祺, 姜波键, 等.基质细胞源性因子-1α/CXC趋化因子受体-4轴经PI3K/Akt通路对胃癌细胞CD133表达的调控作用[J].中华实验外科杂志, 2012, 29(3):378-380.
20.	Chen S, Hou JH, Feng XY, et al.Clinicopathologic significance of putative stem cell marker, CD44 and CD133, in human gastric carcinoma[J].J Surg Oncol, 2013, 107(8):799-806.
21.	Dalerba P, Dylla SJ, Park IK, et al.Phenotypic characterization of human colorectal cancer stem cells[J].Proc Natl Acad Sci U S A, 2007, 104(24):10158-10163.
22.	Ginestier C, Hur MH, Charafe-Jauffret E, et al.ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome[J].Cell Stem Cell, 2007, 1(5):555-567.
23.	Kojima M, Ishii G, Atsumi N, et al.Immunohistochemical dete-ction of CD133 expression in colorectal cancer:a clinicopatholo-gical study[J].Cancer Sci, 2008, 99(8):1578-1583.
24.	Shimada Y, Ishii G, Nagai K, et al.Expression of podoplanin, CD44, and p63 in squamous cell carcinoma of the lung[J].Cancer Sci, 2009, 100(11):2054-2059.
25.	Charafe-Jauffret E, Ginestier C, Iovino F, et al.Aldehyde dehy-drogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer[J].Clin Cancer Res, 2010, 16(1):45-55.

1. Jemal A, Bray F, Center MM, et al.Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
2. Jemal A, Siegel R, Ward E, et al.Cancer statistics[J].CA Cancer J Clin, 2008, 58(2):71-96.
3. Wheelock MJ, Johnson KR.Cadherins as modulators of cellular phenotype[J].Annu Rev Cell Dev Biol, 2003, 19:207-235.
4. Chaffer CL, Weinberg RA.A perspective on cancer cell metastasis[J].Science, 2011, 331(6024):1559-1564.
5. Wakamatsu Y, Sakamoto N, Oo HZ, et al.Expression of cancer stem cell markers ALDH1, CD44, CD133 in primary tumor and lymph node metastasis of gastric cancer[J].Pathol Int, 2012, 62(2):112-119.
6. Rocco A, Liguori E, Pirozzi G, et al.CD133 and CD44 cell surface markers do not identify cancer stem cells in primary human gastric tumors[J].J Cell Physiol, 2012, 227(6):2686-2693.
7. Shi C, Tian R, Wang M, et al.CD44⁺CD133⁺ population exhi-bits cancer stem cell-like characteristics in human gallbladder carc-inoma[J].Cancer Biol Ther, 2010, 10(11):1182-1190.
8. Japanese Gastric Cancer Association.Japanese Classification of Gastric Carcinoma-2nd English Edition[J].Gastric Cancer, 1998, 1(1):10-24.
9. Magee JA, Piskounova E, Morrison SJ.Cancer stem cells:impact, heterogeneity, and uncertainty[J].Cancer Cell, 2012, 21(3):283-296.
10. Bonnet D, Dick JE.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell[J].Nat Med, 1997, 3(7):730-737.
11. Mizrak D, Brittan M, Alison MR.CD133:molecule of the moment[J].J Pathol, 2008, 214(1):3-9.
12. Rajarajan A, Stokes A, Bloor BK, et al.CD44 expression in oro-pharyngeal carcinoma tissues and cell lines[J].PLoS One, 2012, 7(1):e28776.
13. Knutson KL, Lu H, Stone B, et al.Immunoediting of cancers may lead to epithelial to mesenchymal transition[J].J Immunol, 2006, 177(3):1526-1533.
14. Du L, Wang H, He L, et al.CD44 is of functional importance for colorectal cancer stem cells[J].Clin Cancer Res, 2008, 14(21):6751-6760.
15. Haraguchi N, Ohkuma M, Sakashita H, et al.CD133⁺CD44⁺ population efficiently enriches colon cancer initiating cells[J].Ann Surg Oncol, 2008, 15(10):2927-2933.
16. Huang X, Sheng Y, Guan M.Co-expression of stem cell genes CD133 and CD44 in colorectal cancers with early liver metastasis[J].Surg Oncol, 2012, 21(2):103-107.
17. Ponta H, Sherman L, Herrlich PA.CD44:from adhesion molecules to signalling regulators[J].Nat Rev Mol Cell Biol, 2003, 4(1):33-45.
18. Ishimoto T, Oshima H, Oshima M, et al.CD44⁺ slow-cycling tumor cell expansion is triggered by cooperative actions of Wnt and prostaglandin E2 in gastric tumorigenesis[J].Cancer Sci, 2010, 101(3):673-678.
19. 姜海广, 陆瑞祺, 姜波键, 等.基质细胞源性因子-1α/CXC趋化因子受体-4轴经PI3K/Akt通路对胃癌细胞CD133表达的调控作用[J].中华实验外科杂志, 2012, 29(3):378-380.
20. Chen S, Hou JH, Feng XY, et al.Clinicopathologic significance of putative stem cell marker, CD44 and CD133, in human gastric carcinoma[J].J Surg Oncol, 2013, 107(8):799-806.
21. Dalerba P, Dylla SJ, Park IK, et al.Phenotypic characterization of human colorectal cancer stem cells[J].Proc Natl Acad Sci U S A, 2007, 104(24):10158-10163.
22. Ginestier C, Hur MH, Charafe-Jauffret E, et al.ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome[J].Cell Stem Cell, 2007, 1(5):555-567.
23. Kojima M, Ishii G, Atsumi N, et al.Immunohistochemical dete-ction of CD133 expression in colorectal cancer:a clinicopatholo-gical study[J].Cancer Sci, 2008, 99(8):1578-1583.
24. Shimada Y, Ishii G, Nagai K, et al.Expression of podoplanin, CD44, and p63 in squamous cell carcinoma of the lung[J].Cancer Sci, 2009, 100(11):2054-2059.
25. Charafe-Jauffret E, Ginestier C, Iovino F, et al.Aldehyde dehy-drogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer[J].Clin Cancer Res, 2010, 16(1):45-55.

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Expressions of CD133 and CD44 Protein in Primary Lesion of Gastric Cancer and Its Clinical Significance

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