Background. Significances of CD133 mRNA in peripheral blood mononuclear cells (PBMCs) of gastric adenocarcinoma (GC) patients were investigated. Methods. Correlations of CD133 mRNA expression in PBMCs on clinicopathological parameters or CD133 protein expression were analyzed. Receiver operating characteristic curve according to bright scale value (BSV) of CD133 mRNA was used to group patients for prognosis analysis. Results. BSV of preoperative CD133 mRNA in PBMCs in GC was significantly higher than that in volunteers or in GU. Invasive depth or metastatic lymph node number for higher BSV of preoperative CD133 mRNA and invasive depth or lymphatic vessel invasion for higher BSV of postoperative CD133 mRNA in the PBMCs were identified. Patients with CD133+ expression in primary lesion had a significantly higher expression of preoperative CD133 mRNA in the PBMCs. The expression of preoperative or postoperative CD133 mRNA in PBMCs related positively to CD133 mRNA expression in primary lesion. Patients with higher expression of preoperative or postoperative CD133 mRNA shared significantly shorter survival compared with that in lower expression group. Conclusion. Higher levels of preoperative or postoperative CD133 mRNA in PBMCs of GC correlated positively to the lymphatic metastasis and the BSV of CD133 mRNA in primary lesion, indicating the poorer survival. 1. Background Gastric cancer (GC) with only about 20% of overall 5-year survival rate until now is one of the most common forms of cancers worldwide because it is usually diagnosed too late, especially in the developing countries such as China, due to defections of typical symptoms, effectively imaging means and specific tumor biomarkers. Therefore, such advanced cases with later stages of TNM are often unsuitable to receive a curative surgery [1]. Recently, a lot of studies suggested that a small population of cancerous cells named as so-called cancer stem cells (CSCs) with unique self-renewal properties and malignant potentials existed in some sorts of solid tumors [2–4]. As reported, these CSCs could be sorted by flow cytometry or by immunomagnetic separation (IMS) and had been demonstrated to share the stronger abilities of tumorigenicity in vivo and cloning sphere formation in vitro [3–5]. As well known, one of the sorting markers frequently used in the separation/enrichment to these cancerous cells with stemness characteristics in gastrointestinal neoplasm is the cell surface protein nominated as CD133/prominin-1 [5–7]. The accumulated evidence has shown that CD133 as a meaningful marker in the
References
[1]
R. Siegel, D. Naishadham, and A. Jemal, “Cancer statistics, 2012,” CA: Cancer Journal for Clinicians, vol. 62, no. 1, pp. 10–29, 2012.
[2]
H. D. Hemmati, I. Nakano, J. A. Lazareff et al., “Cancerous stem cells can arise from pediatric brain tumors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 25, pp. 15178–15183, 2003.
[3]
A. T. Collins, P. A. Berry, C. Hyde, M. J. Stower, and N. J. Maitland, “Prospective identification of tumorigenic prostate cancer stem cells,” Cancer Research, vol. 65, no. 23, pp. 10946–10951, 2005.
[4]
C. A. O'Brien, A. Pollett, S. Gallinger, and J. E. Dick, “A human colon cancer cell capable of initiating tumour growth in immunodeficient mice,” Nature, vol. 445, no. 7123, pp. 106–110, 2007.
[5]
S. Saigusa, K. Tanaka, Y. Toiyama et al., “Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy,” Annals of Surgical Oncology, vol. 16, no. 12, pp. 3488–3498, 2009.
[6]
H. Yasuda, K. Tanaka, S. Saigusa et al., “Elevated CD133, but not VEGF or EGFR, as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer,” Oncology Reports, vol. 22, no. 4, pp. 709–717, 2009.
[7]
S. Saigusa, K. Tanaka, Y. Toiyama et al., “Immunohistochemical features of CD133 expression: association with resistance to chemoradiotherapy in rectal cancer,” Oncology Reports, vol. 24, no. 2, pp. 345–350, 2010.
[8]
H. Spring, T. Schüler, B. Arnold, G. J. H？mmerling, and R. Ganss, “Chemokines direct endothelial progenitors into tumor neovessels,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 50, pp. 18111–18116, 2005.
[9]
M. Peichev, A. J. Naiyer, D. Pereira et al., “Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors,” Blood, vol. 95, no. 3, pp. 952–958, 2000.
[10]
S. Rafii, D. Lyden, R. Benezra, K. Hattori, and B. Heissig, “Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy?” Nature Reviews Cancer, vol. 2, no. 11, pp. 826–835, 2002.
[11]
B. A. Peters, L. A. Diaz Jr., K. Polyak et al., “Contribution of bone marrow-derived endothelial cells to human tumor vasculature,” Nature Medicine, vol. 11, no. 3, pp. 261–262, 2005.
[12]
B. Dome, J. Timar, J. Dobos et al., “Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer,” Cancer Research, vol. 66, no. 14, pp. 7341–7347, 2006.
[13]
G. Fürstenberger, R. Von Moos, R. Lucas et al., “Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer,” British Journal of Cancer, vol. 94, no. 4, pp. 524–531, 2006.
[14]
D. G. Duda, K. S. Cohen, E. di Tomaso 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,” Journal of Clinical Oncology, vol. 24, no. 9, pp. 1449–1453, 2006.
[15]
M. Boegl and C. Prinz, “CD133 expression in different stages of gastric adenocarcinoma,” British Journal of Cancer, vol. 100, no. 8, pp. 1365–1366, 2009.
[16]
J.-W. Yu, P. Zhang, J.-G. Wu et al., “Expressions and clinical significances of CD133 protein and CD133 mRNA in primary lesion of gastric adenocacinoma,” Journal of Experimental and Clinical Cancer Research, vol. 29, no. 1, article 141, 2010.
[17]
S. Ishigami, S. Ueno, T. Arigami et al., “Prognostic impact of CD133 expression in gastric carcinoma,” Anticancer Research, vol. 30, no. 6, pp. 2453–2457, 2010.
[18]
K. Hibi, M. Sakata, Y.-H. Kitamura et al., “Demethylation of the CD133 gene is frequently detected in early gastric carcinoma,” Anticancer Research, vol. 30, no. 4, pp. 1201–1203, 2010.
[19]
L. M. Smith, A. Nesterova, M. C. Ryan et al., “CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers,” British Journal of Cancer, vol. 99, no. 1, pp. 100–109, 2008.
[20]
L. Wen, X. Z. Chen, K. Yang, et al., “Prognostic value of cancer stem cell marker CD133 expression in gastric cancer: a systematic review,” PLoS ONE, vol. 8, no. 3, Article ID e59154, 2013.
[21]
Y. Wakamatsu, N. Sakamoto, H. Z. Oo et al., “Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer,” Pathology International, vol. 62, no. 2, pp. 112–119, 2012.
[22]
T. Sano and Y. Kodera, “Japanese classification of gastric carcinoma: 3rd English edition,” Gastric Cancer, vol. 14, no. 2, pp. 101–112, 2011.
[23]
J.-W. Yu, J.-G. Wu, Y. Tajima et al., “Study on lymph node metastasis correlated to lymphangiogenesis, lymphatic vessel invasion, and lymph node micrometastasis in gastric cancer,” Journal of Surgical Research, vol. 168, no. 2, pp. 188–196, 2011.
[24]
J.-W. Yu, J.-G. Wu, L.-H. Zheng et al., “Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma,” Journal of Experimental and Clinical Cancer Research, vol. 28, no. 1, article 55, 2009.
[25]
J. R. Siewert, K. B？ttcher, H. J. Stein, and J. D. Roder, “Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer study,” Annals of Surgery, vol. 228, no. 4, pp. 449–461, 1998.
[26]
N. Mehra, M. Penning, J. Maas et al., “Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases,” Clinical Cancer Research, vol. 12, no. 16, pp. 4859–4866, 2006.
[27]
E. H. Lin, M. Hassan, Y. Li et al., “Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence,” Cancer, vol. 110, no. 3, pp. 534–542, 2007.
[28]
H. Iinuma, T. Watanabe, K. Mimori 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,” Journal of Clinical Oncology, vol. 29, no. 12, pp. 1547–1555, 2011.
[29]
K. Nakamura, H. Iinuma, Y. Aoyagi, H. Shibuya, and T. Watanabe, “Predictive value of cancer stem-like cells and cancer-associated genetic markers for peritoneal recurrence of colorectal cancer in patients after curative surgery,” Oncology, vol. 78, no. 5-6, pp. 309–315, 2010.
[30]
Y. Wu, J. Chen, J. Yu, S. Gao, and H. Shen, “A practical scoring system based upon ROC analysis for evaluating potential lymph nodes metastasis during gastric surgery,” Journal of Surgical Oncology, vol. 93, no. 7, pp. 534–540, 2006.
