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肿瘤干细胞标志物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌组织中的表达及临床意义

梁洪享, 钟 竑, 罗 勇, 黄 燕, 丁昭珩, 丁 罡

梁洪享, 钟 竑, 罗 勇, 黄 燕, 丁昭珩, 丁 罡. 肿瘤干细胞标志物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌组织中的表达及临床意义[J]. 肿瘤防治研究, 2013, 40(12): 1138-1142. DOI: 10.3971/j.issn.1000-8578.2013.12.007
引用本文: 梁洪享, 钟 竑, 罗 勇, 黄 燕, 丁昭珩, 丁 罡. 肿瘤干细胞标志物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌组织中的表达及临床意义[J]. 肿瘤防治研究, 2013, 40(12): 1138-1142. DOI: 10.3971/j.issn.1000-8578.2013.12.007
LIANG Hongxiang, ZHONG Hong, LUO Yong, HUANG Yan, DING Zhaoheng, DING Gang. Expression and Signifi cance of Cancer Stem Cell Markers CD133, CD44, SOX2, OCT4 and ALDH1 in Non-small Cell Lung Cancer[J]. Cancer Research on Prevention and Treatment, 2013, 40(12): 1138-1142. DOI: 10.3971/j.issn.1000-8578.2013.12.007
Citation: LIANG Hongxiang, ZHONG Hong, LUO Yong, HUANG Yan, DING Zhaoheng, DING Gang. Expression and Signifi cance of Cancer Stem Cell Markers CD133, CD44, SOX2, OCT4 and ALDH1 in Non-small Cell Lung Cancer[J]. Cancer Research on Prevention and Treatment, 2013, 40(12): 1138-1142. DOI: 10.3971/j.issn.1000-8578.2013.12.007

肿瘤干细胞标志物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌组织中的表达及临床意义

基金项目: 上海市科委资助项目(10411956700)
详细信息
    作者简介:

    梁洪享(1979-),男,硕士在读,主治医师,主要从事肺癌的基础与临床研究

    通讯作者:

    丁罡,E-mail:ddinggang@hotmail.com

  • 中图分类号: R734.2

Expression and Signifi cance of Cancer Stem Cell Markers CD133, CD44, SOX2, OCT4 and ALDH1 in Non-small Cell Lung Cancer

  • 摘要: 目的 研究肿瘤干细胞标记物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌(NSCLC)组织中的表达及临床意义,为探索非小细胞肺癌肿瘤干细胞提供参考。方法 采用免疫组织化学方法检测70例NSCLC 组织、14 例非癌组织中的CD133、CD44、SOX2、OCT4、ALDH1蛋白的表达并对结果进行分析。 结果 (1) CD133、CD44、SOX2、OCT4、ALDH1在70 例NSCLC 组织中的阳性表达率分别为88.57%、98.57%、100%、100%、100%,强阳性表达率分别为48.57%、67.14%、67.14%、31.43%、50%;CD133、CCD44在NSCLC与非癌组织中的表达差异存在统计学意义( P 均<0.0001),SOX2、OCT4、ALDH1在NSCLC与非癌组织中的表达差异无统计学意义(P均>0.05)。(2)随着病理级别的升高,CD133、CD44、SOX2、OCT4及ALDH1 的表达呈上升趋势,分化越低的NSCLC表达上述指标的概率越高,其中CD133、SOX2、OCT4的表达在高、中、低分化组织中差异存在统计学意义(P值分别为0.001、0.040、<0.0001);CD133的表达在吸烟史、分化程度、淋巴结转移、肿瘤分期四个因素上差异存在统计学意义(P值分别为0.033、0.001、0.033、0.046);CD44与SOX2的表达在年龄上的差异存在统计学意义(P值分别为0.001、0.040)。 结论 NSCLC组织中CD133、CD44、SOX2、OCT4、ALDH1阳性率高,CD133、CD44的表达明显高于非癌组织;CD133、SOX2、OCT4与NSCLC的恶性程度有关;CD44与SOX2与年龄因素有关。

     

    Abstract: Objective To investigate the expression and signifi cance of cancer stem cell markers CD133, CD44, SOX2, OCT4, ALDH1 in non-small cell lung carcinoma( NSCLC) and to look for cancer stem cells of NSCLC. Methods Seventy cases of NSCLC tissues and 14 cases of non cancer tissues were detected by immunohistochemistry for CD133, CD44, SOX2, OCT4 and ALDH1. Results Seventy NSCLC tissues, The positive expression rates of CD133, CD44, SOX2, OCT4 and ALDH1 were 88.57%, 98.57%, 100%, 100% and 100%,respectively. And strong positive expression rates were 48.57%, 67.14%, 67.14%, 31.43% and 50% respectively. The expression rates of CD133 and CD44 were signifi cantly higher than those in non cancer tissues (P<0.0001) ; The expression rates of SOX2, OCT4 and ALDH1 showed no significant difference between NSCLC and non cancer tissues (P>0.05). The expressions of CD133, CD44, SOX2, OCT4 and ALDH1 were increased along with the pathology grades. The expressions of CD133, SOX2 and OCT4 were signifi cantly higher in poor differentiated than those in the well differentiated (P=0.001,0.040 and <0.0001). The expression of CD133 was significant difference (P=0.033, 0.001, 0.033, 0.046, P<0.05 )in smoking history, differentiation, lymph node metastasis, staging factors. The expressions of CD44 and SOX2 were signifi cant difference in age (P=0.001,0.040). Conclusion The positive expression rates of CD133, CD44, SOX2, OCT4 and ALDH1 were increased,and CD133 and CD44 expressions in NSCLC were signifi cantly higher than those of non cancer tissue. CD133, SOX2 and OCT4 were associated with historical types and CD44 and SOX2 with ages.

     

  • [1] Xu XZ, Tong WM, Li J,et al.The molecular basis of cancer[M].3rd Edition.Beijing:Press of Science and Technology,2011:113-4.[许 兴智,佟伟民,李静,等.癌症的分子基础[M].第3版.北京:科技出 版社,2011:113-4.]
    [2] Terpe HJ, Störkel S, Zimmer U, et al. Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor differentiation[J]. Am J Pathol,1996,148(2):453-63.
    [3] Xu LZ, Yang WT. The criterion standard resultant of immunohistochemistry[J]. Zhongguo Ai Zheng Za Zhi, 19 96,6(4):229-30.[许良中,杨文涛.免疫组织化学反应结果的判 断标准[J].中国癌症杂志, 1996,6(4):229-31.]
    [4] Horst D, Kriegl L, Engel J, et al.CD133 expression is an independent prognostic marker for low survival in colorectal cancer[J].Br J Cancer,2008,99(8):1285-9.
    [5] Reya T,Morrison SJ,Clarke MF,et al. Stem cells, cancer, and cancer stem cells[J].Nature,2001,414(6859):105-11.
    [6] Sakashita H, Ieta K, Haraguchi N, et al. Cancer stem cell[J]. Gan To Kagaku Ryoho, 2007,34(11):1721-9.
    [7] Jiang Y, Liu YY, Zuo PP. Application of cancer stem cell theory in research of non-small cell lung cancer[J].Yi Xue Zong Shu,2011,17(1):56-61. [姜尧,刘雁勇,左萍萍. 肿瘤干细胞学说 在非小细胞肺癌研究中的应用[J].医学综述,2011,17(1):56-61.]
    [8] Miyamoto T, Weissman IL, Akashi K. AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8; 21 chromosomal translocation[J].Proc Natl Acad Sci U S A, 20 00,97(13):7521-6.
    [9] Singh SK, Hawkins C, Clarke ID, et al. Identifi cation of human brain tumor initiating cells[J].Nature,2004,432(7015):396-401.
    [10] Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells[J]. Proc Natl Acad Sci U S A, 2003,100(7):3983-8.
    [11] Croker AK, Goodale D, Chu J, et al. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability [J]. J Cell Mol Med, 2009,13(8B):2236-52.
    [12] Yuan Y, Zhong H. The progression of induced pluripotent stem cells[J].Shi Yong Yi Xue Za Zhi,2010,26(6): 897-9.[袁源,钟竑.诱 导多能干细胞的研究进展[J].实用医学杂志,2010,26(6): 897-9.]
    [13] Tirino V, Camerlingo R, Franco R, et al. The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer[J]. Eur J Cardiothorac Surg, 20 09,36(3):446-53.
    [14] Liu D, Li WM, Mo XM, et al. Multiparametric flow cytometry analyzes the expressions of immunophenotype CD133, CD34, CD44 in lung cancer naive cells[J].Sichuan Da Xue Xue Bao Yi Xue Ban,2008,39(5):827-31.[刘丹,李为民,莫显民,等. 多参数流 式细胞术分析肺癌幼稚细胞免疫表型CD133、CD34、CD44 的表达[J].四川大学学报(医学版) ,2008,39(5):827-31.]
    [15] Bertolini G, Roz L, Perego P, et al. Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment[J].Proc Natl Acad Sci U S A, 20 09,106(38):16281-6.
    [16] Meng X, Li M, Wang X, et al. Both CD133+ and CD133- subpopulations of A549 and H446 cells contain cancer-initiating cells[J].Cancer Sci, 2009,100(6):1040-6.
    [17] Leung EL, Fiscus RR, Tung JW, et al. Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties[J]. PLoS One, 2010,5(11):e14062.
    [18] Lu ZQ, Li HG, Zhang HZ, et al. Expression and significance of CD44(+)ESA(+)CD24(-/low), stem cell markers for breast cancer, in non-small-cell lung carcinoma[J].Ai Zheng, 20 08,27(6):575-9.[吕志强,李海刚,张惠忠,等. 乳腺癌肿瘤干细 胞标记物CD44+ESA+CD24-/low在非小细胞肺癌组织中的表 达及其意义[J].癌症, 2008,27(6):575-9.]
    [19] 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):2054-9.
    [20] Sholl LM, Long KB, Hornick JL. Sox2 expression in pulmonary non-small cell and neuroendocrine carcinomas[J]. Appl Immunohistochem Mol Morphol, 2010,18(1):55-61.
    [21] Karoubi G, Cortes-Dericks L, Gugger M, et al. Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma[J].J Surg Oncol, 2010,102(6):689-98.
    [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):555-67.
    [23] Heerma van Voss MR, van der Groep P, Bart J,et al. Expression of the stem cell marker ALDH1 in BRCA1 related breast cancer[J]. Cell Oncol (Dordr), 2011,34(1):3-10.
    [24] Liu DC, Yang ZL, Jiang S. Identifi cation of musashi-1 and ALDH1 as carcinogenesis, progression, and poor-prognosis related biomarkers for gallbladder adenocarcinoma[J]. Cancer Biomark, 20 10-2011,8(3):113-21.
    [25] Doherty RE, Haywood-Small SL, Sisley K, et al. Aldehyde dehydrogenase activity selects for the holoclone phenotype in prostate cancer cells[J]. Biochem Biophys Res Commun, 20 11,414(4):801-7.
    [26] Kahlert C, Bergmann F, Beck J,et al. Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer[J]. BMC Cancer, 2011,11:275.
    [27] Sullivan JP, Spinola M, Dodge M,et al. Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling[J]. Cancer Res, 2010,70(23):9937-48.
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出版历程
  • 收稿日期:  2013-01-23
  • 修回日期:  2013-03-28
  • 刊出日期:  2013-12-24

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