Expression of CD133 in Gastric Adenocarcinoma Tissue and Its Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WU Jugang , YU Jiwei , LU Ruiqi , JIANG Haiguang , ZHOU Guocai , ZHENG Linhai , JIANG Bojian

Department of General Surgery，No. 3 People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine， Shanghai 201900， China;

Corresponding author：

Keywords：

Gastric cancer; CD133; Lymph node metastasis

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Objective 　To study the expression of CD133 mRNA in peripheral blood mononuclear cells （PBMCs） of patients with gastric adenocarcinoma （GC） before operation or after operation and its clinical significance. To learn the relationship of CD133 expressions in PBMCs to primary lesion of GC.
Methods 　Fifty patients with GC，10 patients with gastric ulcer （GU）， and 10 healthy volunteers were registered in this research. Expressions of CD133 mRNA in PBMCs and in primary lesion of GC by semi-quantitative RT-PCR and expression of CD133 protein in primary lesion of GC by immunohistochemical staining were detected. Correlations of CD133 mRNA expression with clinicopathologic parameters and postoperative survival rate were analyzed. Relation between CD133 mRNA level and CD133 protein expression or lymphatic metastasis were assessed too.
Results 　The brightness scale value （ABSV） of CD133 mRNA in PBMCs of the patients with GC before operation （0.270±0.163） was higher than that in the healthy volunteers （0.029±0.060） or in the patients with GU （0.059±0.099）（P=0.000）. The ABSV of CD133 mRNA in the PBMCs of patients with GC before operation was related to poor cell differentiation （P=0.002）， lymph vessel invasion （P=0.028），deeper tumor invasion （P=0.041），later lymph node metastasis stage （P=0.010），later TNM stage （P=0.006），and positive expression of CD133 protein in the primary lesion （P=0.011）. Relative analysis revealed that the ABSV of CD133 mRNA in the PBMCs of patients with GC before operation was related positively to metastatic lymphatic nodes ratio （rs=0.422，P=0.002），metastatic lymph node number （rs=0.398，P=0.004），and ABSV of CD133 mRNA in the primary lesion of GC （rs=0.337，P=0.017）. The ABSV of CD133 mRNA in the PBMCs of patients with GC after operation obtained from blood sample at 1 week after curative resection was higher than that in the patients before operation （P=0.021）. Patients suffered from deeper invasion inclined to have a higher ABSV of CD133 mRNA after surgery （P=0.039）. Higher expression of CD133 mRNA in patients after operation demonstrated a much poorer survival rate （P=0.013）.
Conclusions 　Higher expressive level of CD133 mRNA in GC before operation is associated to poor cell differentiation，lymph vessel invasion，deeper invasion，higher lymph node metastasis，later TNM stage，and positive expression of CD133 protein. It is also related positively to metastatic lymphatic nodes ratio，metastatic lymph node number，and ABSV of CD133 mRNA in primary lesion of GC. The level of CD133 mRNA in PBMCs of patients with GC is higher after operation as compared with before operation，which demonstrates deeper invasion and poorer survival.

Citation： WU Jugang,YU Jiwei,LU Ruiqi,JIANG Haiguang,ZHOU Guocai,ZHENG Linhai,JIANG Bojian,.. Expression of CD133 in Gastric Adenocarcinoma Tissue and Its Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(8): 831-837. doi: Copy

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19.	唐毕锋，马立业，翟羽佳，等. 肿瘤干细胞标志物CD133在胃癌中的表达及其临床意义[J]. 临床肿瘤学杂志， 2008， 78(6)：495-498.
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25.	Iinuma H， Watanabe T， Mimori K， et al. Clinical significance of circulating tumor cells， including cancer stem-like cells， in peripheral blood for recurrence and prognosis in patients with Dukes’stage B and C colorectal cancer[J]. J Clin Oncol， 2011， 29(12)：1547-1555.
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1. Siegel R， Naishadham D， Jemal A. Cancer statistics， 2012[J]. CA Cancer J Clin， 2012， 62(1)：10-29.
2. Hemmati HD， Nakano I， Lazareff JA， et al. Cancerous stem cells can arise from pediatric brain tumors[J]. Proc Natl Acad Sci USA， 2003， 100(25)：15178-15183.
3. Collins AT， Berry PA， Hyde C， et al. Prospective identification of tumorigenic prostate cancer stem cells[J]. Cancer Res， 2005， 65(23)：10946-10951.
4. O’Brien CA， Pollett A， Gallinger S， et al. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice[J]. Nature， 2007， 445(7123)：106-110.
5. Saigusa S， Tanaka K， Toiyama Y， et al. Correlation of CD133， OCT4， and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy[J]. Ann Surg Oncol， 2009， 16(12)：3488-3498.
6. Yusuda H， Tanaka K， Saigusa S， et al. Elevated CD133， but not VEGF or EGFR， as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer[J]. Oncol Rep， 2009， 22(4)：709-717.
7. Saigusa S， Tanaka K， Toiyama Y， et al. Immunohistochemical features of CD133 expression：association with resistance to chemoradiotherapy in rectal cancer[J]. Oncol Rep， 2010， 24(2)：345-350.
8. Spring H， Schüler T， Arnold B， et al. Chemokines direct endothelial progenitors into tumor neovessels[J]. Proc Natl Acad Sci USA， 2005， 102(50)：18111-18116.
9. Peichev M， Naiyer AJ， Pereira D， et al. Expression of VEGFR-2 and AC133 by circulating human CD34(＋) cells identifies a population of functional endothelial precursors[J]. Blood， 2000， 95(3)：952-958.
10. Rafii S， Lyden D， Benezra R， et al. Vascular and haematopoietic stem cells：novel targets for anti-angiogenesis therapy?[J]. Nat Rev Cancer， 2002， 2(11)：826-835.
11. Peters BA， Diaz LA， Polyak K， et al. Contribution of bone marrow-derived endothelial cells to human tumor vasculature[J]. Nat Med， 2005， 11(3)：261-262.
12. Dome B， Timar J， Dobos J， et al. Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer[J]. Cancer Res， 2006， 66(14)：7341-7347.
13. Fürstenberger G， von Moos R， Lucas R， et al. Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer[J]. Br J Cancer， 2006， 94(4)：524-531.
14. Duda DG， Cohen KS， di Tomaso E， et al. Differential CD146 expression on circulating versus tissue endothelial cells in rectal cancer patients：implications for circulating endothelial and progenitor cells as biomarkers for antiangiogenic therapy[J]. J Clin Oncol， 2006， 24(9)：1449-1453.
15. Boegl M， Prinz C. CD133 expression in different stages of gastric adenocarcinoma[J]. Br J Cancer， 2009， 100(8)：1365-1366.
16. 张鹏，吴巨钢，姜波健，等. 胃癌组织中CD133 mRNA表达与临床病理特征的关系[J]. 上海交通大学学报(医学版)， 2010， 30(2)：213-217.
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]. J Exp Clin Cancer Res， 2010， 29(1)：141.
18. 李亚卓，王凤华，赵坡. CD133、Ki-67在胃癌的表达及临床病理意义[J]. 世界华人消化杂志， 2008， 16(28)：3167-3171.
19. 唐毕锋，马立业，翟羽佳，等. 肿瘤干细胞标志物CD133在胃癌中的表达及其临床意义[J]. 临床肿瘤学杂志， 2008， 78(6)：495-498.
20. 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[J]. Br J Cancer， 2008， 99(1)：100-109.
21. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma - 2nd English edition -[J]. Gastric Cancer， 1998， 1(1)：10-24.
22. Yu JW， Wu JG， Zheng LH， et al. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma[J]. J Exp Clin Cancer Res， 2009， 28(28)：55.
23. Mehra N， Penning M， Maas J， et al. Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases[J]. Clin Cancer Res， 2006， 12(16)：4859-4866.
24. Lin EH， Hassan M， Li Y， et al. Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence[J]. Cancer， 2007， 110(3)：534-542.
25. Iinuma H， Watanabe T， Mimori K， et al. Clinical significance of circulating tumor cells， including cancer stem-like cells， in peripheral blood for recurrence and prognosis in patients with Dukes’stage B and C colorectal cancer[J]. J Clin Oncol， 2011， 29(12)：1547-1555.
26. Nakamura K， Iinuma H， Aoyagi Y， et al. Predictive value of cancer stem-like cells and cancer-associated genetic markers for peritoneal recurrence of colorectal cancer in patients after curative surgery[J]. Oncology， 2010， 78(5-6)：309-315.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of CD133 in Gastric Adenocarcinoma Tissue and Its Clinical Significance

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