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肝癌组织中CD68+肿瘤相关巨噬细胞数量与Ki-67蛋白表达及原发性肝癌预后的关系

陈利君, 陈静琦, 曾波航

陈利君, 陈静琦, 曾波航. 肝癌组织中CD68+肿瘤相关巨噬细胞数量与Ki-67蛋白表达及原发性肝癌预后的关系[J]. 肿瘤防治研究, 2016, 43(9): 774-778. DOI: 10.3971/j.issn.1000-8578.2016.09.009
引用本文: 陈利君, 陈静琦, 曾波航. 肝癌组织中CD68+肿瘤相关巨噬细胞数量与Ki-67蛋白表达及原发性肝癌预后的关系[J]. 肿瘤防治研究, 2016, 43(9): 774-778. DOI: 10.3971/j.issn.1000-8578.2016.09.009
CHEN Lijun, CHEN Jingqi, ZENG Bohang. Correlation of CD68+ Tumor-associated Macrophages Number with Ki-67 Expression and Prognosis of Patients with Primary Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2016, 43(9): 774-778. DOI: 10.3971/j.issn.1000-8578.2016.09.009
Citation: CHEN Lijun, CHEN Jingqi, ZENG Bohang. Correlation of CD68+ Tumor-associated Macrophages Number with Ki-67 Expression and Prognosis of Patients with Primary Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2016, 43(9): 774-778. DOI: 10.3971/j.issn.1000-8578.2016.09.009

肝癌组织中CD68+肿瘤相关巨噬细胞数量与Ki-67蛋白表达及原发性肝癌预后的关系

基金项目: 

国家自然科学基金 81272900,81172537

详细信息
    作者简介:

    陈利君(1988-),女,硕士,医师,主要从事肿瘤个体化治疗的研究

    通讯作者:

    陈静琦: 曾波航.E-mail: zengbh63@163.com

  • 中图分类号: R735.7

Correlation of CD68+ Tumor-associated Macrophages Number with Ki-67 Expression and Prognosis of Patients with Primary Hepatocellular Carcinoma

More Information
  • 摘要:
    目的 

    探讨原发性肝癌(HCC)患者肝癌组织中CD68+肿瘤相关巨噬细胞(CD68+ TAM)的数量与增殖指标Ki-67及肝癌预后的关系,寻找评估肝癌预后更可靠的指标。

    方法 

    应用免疫组织化学SABC法检测73例HCC组织中CD68+ TAM的分布情况及增殖指标Ki-67蛋白表达,运用化学发光测定法检测血清AFP水平。

    结果 

    CD68+ TAM高密度组Ki-67阳性率明显高于低密度组(P=0.0191)。CD68+ TAM数量与HCC患者的年龄、性别无关(P>0.05),而与HCC病理分级有关(P=2.83E-04)。血清AFP水平与HCC患者的年龄、性别、病理分级无关(P>0.05)。CD68+ TAM高密度组的总生存时间显著短于低密度组(P=0.0004)。而AFP高水平组与低水平组比较,总生存时间、Ki-67阳性率差异均无统计学意义(P>0.05)。

    结论 

    HCC患者肝癌组织中CD68+ TAM数量与肝癌增殖活性密切相关,是HCC预后的独立危险因素。与AFP相比,CD68+ TAM有望成为评估肝癌预后更可靠的指标。

     

    Abstract:
    Objective 

    To determine a reliable prognostic marker for hepatocellular carcinoma(HCC), we investigated the prognostic significance of the relationship between the number of CD68+ tumor-associated macrophages(TAM) and Ki-67.

    Methods 

    SABC immunohistochemistry was used to observe the distribution of TAM marker CD68+ and the protein expression of proliferation index Ki-67 in HCC tissues from 73 patients who had complete histories and were followed up for more than five years. AFP in those patients’ serums was detected by chemiluminescent immunoassay(CLIA).

    Results 

    The positive rate of Ki-67 was significantly higher in CD68+ high-density group, compared with CD68+ low-density group (P=0.0191). There was no correlation between the number of CD68+ TAM and age, gender(P>0.05). The number of CD68+ TAM was correlated positively with histological grade(P=2.83E-04). However, no correlation between the serum AFP level and age, gender or histological grade was observed(P>0.05). The overall survival (OS) in high CD68+ TAM group was significantly shorter than that in low CD68+ TAM group (P=0.0004). Nevertheless, no statistical significance was found in OS or Ki-67 positive rate between high AFP and low AFP group (P>0.05).

    Conclusion 

    CD68+ TAM number is closely correlated with HCC proliferation activity and is an independent risk factor for HCC prognosis. Compared with AFP, CD68+ TAM might serve as a prognostic marker for HCC.

     

  • 图  1   CD68+ TAMs在肝癌不同病理分级中的分布

    Figure  1   Distribution of CD68+ TAMs in different histological grades of HCC

    图  2   CD68+ TAMs数量、AFP水平与Ki-67的关系

    Figure  2   Correlation of CD68+ TAMs number,AFP level with Ki-67 positive rate

    图  3   HCC组织CD68+TAMs高低密度组(A)和AFP高低水平组(B)生存曲线比较

    Figure  3   Comparison of overall survival curves base on CD68+ TAMs density(A) and AFP level(B)

    表  1   TAMs数量与HCC患者临床病理特征的关系

    Table  1   Correlation of CD68+ TAMs number with clinicopathological status of HCC patients

    下载: 导出CSV

    表  2   AFP水平与HCC患者临床病理特征的关系

    Table  2   Correlation of AFP level with clinicopathological status of HCC patients

    下载: 导出CSV

    表  3   Cox回归模型生存分析比较

    Table  3   Cox regression model test for survival of HCC patients

    下载: 导出CSV
  • [1] Coffelt SB, Hughes R, Lewis CE. Tumor-associated macrophages: effectors of angiogenesis and tumor progression[J]. Biochim Biophys Acta, 2009, 1796(1): 11-8.
    [1]

    Coffelt SB, Hughes R, Lewis CE. Tumor-associated macrophages: effectors of angiogenesis and tumor progression[J]. Biochim Biophys Acta, 2009, 1796(1): 11-8. http://cn.bing.com/academic/profile?id=2098533764&encoded=0&v=paper_preview&mkt=zh-cn

    [2]

    Quatromoni JG, Eruslanov E. Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer[J]. Am J Transl Res, 2012, 4(4): 376-89. http://cn.bing.com/academic/profile?id=1483271435&encoded=0&v=paper_preview&mkt=zh-cn

    [2] Quatromoni JG, Eruslanov E. Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer[J]. Am J Transl Res, 2012, 4(4): 376-89.
    [3]

    Sica A, Schioppa T, Mantovani A, et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy[J]. Eur J Cancer, 2006, 42(6): 717-27. doi: 10.1016/j.ejca.2006.01.003

    [3] Sica A, Schioppa T, Mantovani A, et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy[J]. Eur J Cancer, 2006, 42(6): 717-27.
    [4] Chen J, Yao Y, Gong C, et al. CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3[J]. Cancer Cell, 2011, 19(4): 541-55.
    [4]

    Chen J, Yao Y, Gong C, et al. CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3[J]. Cancer Cell, 2011, 19(4): 541-55. doi: 10.1016/j.ccr.2011.02.006

    [5] Yang QL. The correlation of CD+68macrophage expression with the prognosis of hepatocellular carcinoma[J]. Zhongguo Zhong Liu Lin Chuang Yu Kang Fu, 2013, 20(12): 1322-4. http://www.cnki.com.cn/Article/CJFDTOTAL-ZGZK201312004.htm

    杨全良. 巨噬细胞在肝细胞癌中的分布及与预后的相关性[J]. 中国肿瘤临床与康复, 2013, 20(12): 1322-4. http://www.cnki.com.cn/Article/CJFDTOTAL-ZGZK201312004.htm

    [5] 杨全良. 巨噬细胞在肝细胞癌中的分布及与预后的相关性[J]. 中国肿瘤临床与康复, 2013, 20(12): 1322-4. [Yang QL. The correlation of CD+68macrophage expression with the prognosis of hepatocellular carcinoma[J]. Zhongguo Zhong Liu Lin Chuang Yu Kang Fu, 2013, 20(12): 1322-4.]
    [6]

    Jun CH, Ki HS, Lee HK, et al. Clinical significance and risk factors of postembolization fever in patients with hepatocellular carcinoma[J]. World J Gastroenterol, 2013, 19(2): 284-9. doi: 10.3748/wjg.v19.i2.284

    [6] Jun CH, Ki HS, Lee HK, et al. Clinical significance and risk factors of postembolization fever in patients with hepatocellular carcinoma[J]. World J Gastroenterol, 2013, 19(2): 284-9.
    [7]

    Butterfield LH, Ribas A, Dissette VB, et al. A phase Ⅰ/Ⅱ trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides[J]. Clin Cancer Res, 2006, 12(9): 2817-25. doi: 10.1158/1078-0432.CCR-05-2856

    [7] Butterfield LH, Ribas A, Dissette VB, et al. A phase Ⅰ/Ⅱ trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides[J]. Clin Cancer Res, 2006, 12(9): 2817-25.
    [8] Ma WJ, Wang HY, Teng LS. Correlation analysis of preoperative serum alpha-fetoprotein(AFP) level and prognosis of hepatocellular carcinoma(HCC) after hepatectomy[J]. World J Surg Oncol, 2013, 11: 212.
    [8]

    Ma WJ, Wang HY, Teng LS. Correlation analysis of preoperative serum alpha-fetoprotein(AFP) level and prognosis of hepatocellular carcinoma(HCC) after hepatectomy[J]. World J Surg Oncol, 2013, 11: 212. doi: 10.1186/1477-7819-11-212

    [9] 邵珊珊. AFP阴性肝细胞癌患者外周血GPC3mRNA的表达[D]. 青岛大学, 2014. http://cdmd.cnki.com.cn/Article/CDMD-11065-1014302619.htm

    Shao SS. Expression of GPC3mRNA in peripheral blood of patients with AFP negative hepatocellular carcinoma[D]. Qingdao Da Xue, 2014. http://cdmd.cnki.com.cn/Article/CDMD-11065-1014302619.htm

    [9] 邵珊珊. AFP阴性肝细胞癌患者外周血GPC3mRNA的表达 [D] 青岛大学, 2014. [Shao SS. Expression of GPC3mRNA in peripheral blood of patients with AFP negative hepatocellular carcinoma[D]. Qingdao Da Xue, 2014.]
    [10] Park H, Park JY. Clinical significance of AFP and PIVKA-Ⅱ responses for monitoring treatment outcomes and predicting prognosis in patients with hepatocellular carcinoma[J]. Biomed Res Int, 2013, 2013: 310427.
    [10]

    Park H, Park JY. Clinical significance of AFP and PIVKA-Ⅱ responses for monitoring treatment outcomes and predicting prognosis in patients with hepatocellular carcinoma[J]. Biomed Res Int, 2013, 2013: 310427. http://cn.bing.com/academic/profile?id=2045174122&encoded=0&v=paper_preview&mkt=zh-cn

    [11] 靳向前. 原发性肝癌预后因素的相关性分析[D]. 广州中医药大学, 2010. http://cdmd.cnki.com.cn/article/cdmd-10572-2010125413.htm

    Jin XQ. Correlation analysis of prognostic factors in patients with primary liver cancer[D]. Guangzhou Zhong Yi Yao Da Xue, 2010. http://cdmd.cnki.com.cn/article/cdmd-10572-2010125413.htm

    [11] 靳向前. 原发性肝癌预后因素的相关性分析[D]. 广州中医药大 学, 2010. [Jin XQ. Correlation analysis of prognostic factors in patients with primary liver cancer[D]. Guangzhou Zhong Yi Yao Da Xue, 2010.]
    [12] 解瑞玲, 董伯升, 成媛, 等. CD68、CD163阳性巨噬细胞在食 管癌组织浸润及对预后的影响[J]. 第三军医大学学报, 2011, 33 (5): 523-6. [Xie RL, Dong BS, Cheng Y, et al. Infiltrations of CD68 and CD163 positive macrophages in esophageal cancer tissue and their impacts on prognosis[J]. Di San Jun Yi Da Xue Xue Bao, 2011, 33(5): 523-6.]
    [12] 解瑞玲, 董伯升, 成媛, 等. CD68、CD163阳性巨噬细胞在食管癌组织浸润及对预后的影响[J]. 第三军医大学学报, 2011, 33(5): 523-6. http://www.cnki.com.cn/Article/CJFDTOTAL-DSDX201105028.htm

    Xie RL, Dong BS, Cheng Y, et al. Infiltrations of CD68 and CD163 positive macrophages in esophageal cancer tissue and their impacts on prognosis[J]. Di San Jun Yi Da Xue Xue Bao, 2011, 33(5): 523-6. http://www.cnki.com.cn/Article/CJFDTOTAL-DSDX201105028.htm

    [13] 杨卫军, 董浩林, 吴正阳, 等. CD68在胃癌组织中表达的意义 [J] 检验医学与临床, 2013, 10(19): 2528-9. [Yang WJ, Dong HL, Wu ZY, et al. Significance of CD68 expression in gastric cancer tissue[J]. Jian Yan Yi Xue Yu Lin Chuang, 2013, 10(19): 2528-9.]
    [13] 杨卫军, 董浩林, 吴正阳, 等. CD68在胃癌组织中表达的意义[J]. 检验医学与临床, 2013, 10(19): 2528-9. http://www.cnki.com.cn/Article/CJFDTOTAL-JYYL201319014.htm

    Yang WJ, Dong HL, Wu ZY, et al. Significance of CD68 expression in gastric cancer tissue[J]. Jian Yan Yi Xue Yu Lin Chuang, 2013, 10(19): 2528-9. http://www.cnki.com.cn/Article/CJFDTOTAL-JYYL201319014.htm

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出版历程
  • 收稿日期:  2015-10-14
  • 修回日期:  2016-04-08
  • 网络出版日期:  2024-02-04
  • 刊出日期:  2016-08-31

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