• 上海交通大學(xué)醫(yī)學(xué)院附屬第三人民醫(yī)院普外科(上海 201900);

目的  研究胃癌組織中CD133表達(dá)的相互關(guān)系,重點(diǎn)明確術(shù)前、術(shù)后外周血單核細(xì)胞中CD133 mRNA表達(dá)的臨床意義及其與胃癌原發(fā)灶CD133表達(dá)的關(guān)系。
方法  50例胃癌、10例胃潰瘍穿孔及10名健康自愿者入組研究。胃癌患者術(shù)前和術(shù)后1周抽外周靜脈血各4ml,密度梯度離心法分離單核細(xì)胞,半定量逆轉(zhuǎn)錄聚合酶鏈反應(yīng)(RT-PCR)檢測(cè)CD133mRNA表達(dá)水平。胃潰瘍穿孔患者術(shù)前抽外周靜脈血、健康自愿者抽晨血各4ml。胃癌原發(fā)灶及癌旁正常胃黏膜組織分別行RT-PCR、免疫組織化學(xué)染色檢測(cè)CD133mRNA和蛋白的表達(dá)。分析CD133表達(dá)對(duì)各臨床病理特征和預(yù)后的影響。
結(jié)果  健康自愿者及術(shù)前胃潰瘍患者及胃癌患者外周血中CD133mRNA的半定量值分別為0.029±0.060、0.059±0.099及0.270±0.163 (P=0.000)。胃癌患者術(shù)前外周血CD133mRNA表達(dá)與腫瘤組織分化程度、淋巴管浸潤(rùn)、腫瘤浸潤(rùn)深度、淋巴結(jié)轉(zhuǎn)移及TNM分期均有關(guān)(P<0.05)。相關(guān)分析顯示,胃癌患者術(shù)前外周血中CD133mRNA半定量值與淋巴結(jié)轉(zhuǎn)移率(rs=0.422,P=0.002)、癌轉(zhuǎn)移淋巴結(jié)枚數(shù)(rs=0.398,P=0.004)呈正相關(guān),并與胃癌原發(fā)灶中CD133mRNA的表達(dá)呈正相關(guān)(rs=0.337,P=0.017)。胃癌原發(fā)灶中CD133蛋白表達(dá)陽(yáng)性者,術(shù)前外周血中CD133mRNA的半定量值較CD133蛋白表達(dá)陰性者高(Z=-2.539,P=0.011)。50例胃癌患者行胃癌根治術(shù)后1周,其外周血中CD133mRNA半定量值明顯高于術(shù)前CD133mRNA的表達(dá)水平(P=0.021)。胃癌浸潤(rùn)深度較深者,術(shù)后CD133mRNA表達(dá)升高更明顯(Z=-1.978,P=0.039)。術(shù)后外周血中CD133mRNA高表達(dá)者較低表達(dá)者預(yù)后更差(χ2=6.193,P=0.013)。
結(jié)論  胃癌患者術(shù)前外周血高表達(dá)CD133mRNA,其與腫瘤分化程度、淋巴管浸潤(rùn)、腫瘤浸潤(rùn)深度、淋巴結(jié)轉(zhuǎn)移、TNM分期及胃癌原發(fā)病灶CD133蛋白表達(dá)有關(guān),且與淋巴結(jié)轉(zhuǎn)移率、癌轉(zhuǎn)移淋巴結(jié)枚數(shù)及胃癌原發(fā)灶中CD133mRNA的表達(dá)呈正相關(guān)。術(shù)后患者外周血中CD133mRNA半定量值較術(shù)前明顯升高,這一升高提示腫瘤浸潤(rùn)程度較深,患者預(yù)后較差。

引用本文: 吳巨鋼,俞繼衛(wèi),陸瑞祺,姜海廣,周國(guó)才,鄭林海,姜波健. 胃癌組織中CD133 的表達(dá)及其臨床意義△. 中國(guó)普外基礎(chǔ)與臨床雜志, 2012, 19(8): 831-837. doi: 復(fù)制

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. 張鵬, 吳巨鋼, 姜波健, 等. 胃癌組織中CD133 mRNA表達(dá)與臨床病理特征的關(guān)系[J]. 上海交通大學(xué)學(xué)報(bào)(醫(yī)學(xué)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. 李亞卓, 王鳳華, 趙坡. CD133、Ki-67在胃癌的表達(dá)及臨床病理意義[J]. 世界華人消化雜志, 2008, 16(28):3167-3171.
19. 唐畢鋒, 馬立業(yè), 翟羽佳, 等. 腫瘤干細(xì)胞標(biāo)志物CD133在胃癌中的表達(dá)及其臨床意義[J]. 臨床腫瘤學(xué)雜志, 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.
  1. 1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012[J]. CA Cancer J Clin, 2012, 62(1):10-29.
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 15. Boegl M, Prinz C. CD133 expression in different stages of gastric adenocarcinoma[J]. Br J Cancer, 2009, 100(8):1365-1366.
  16. 16. 張鵬, 吳巨鋼, 姜波健, 等. 胃癌組織中CD133 mRNA表達(dá)與臨床病理特征的關(guān)系[J]. 上海交通大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2010, 30(2):213-217.
  17. 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. 18. 李亞卓, 王鳳華, 趙坡. CD133、Ki-67在胃癌的表達(dá)及臨床病理意義[J]. 世界華人消化雜志, 2008, 16(28):3167-3171.
  19. 19. 唐畢鋒, 馬立業(yè), 翟羽佳, 等. 腫瘤干細(xì)胞標(biāo)志物CD133在胃癌中的表達(dá)及其臨床意義[J]. 臨床腫瘤學(xué)雜志, 2008, 78(6):495-498.
  20. 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. 21. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma - 2nd English edition -[J]. Gastric Cancer, 1998, 1(1):10-24.
  22. 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. 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. 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. 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. 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.