CD133对于肝癌患者预后意义的Meta分析

张舜柏; 王志强; 张海鸿

PDF(2236 KB)

湖南师范大学学报医学版 ›› 2023, Vol. 20 ›› Issue (2) : 130-139.

临床医学

CD133对于肝癌患者预后意义的Meta分析

张舜柏, 王志强, 张海鸿

作者信息 +

Meta-analysis of CD133 on the prognosis of patients with hepatocellular carcinoma

Zhang Shunbai, Wang Zhiqiang, Zhang Haihong

Author information +

文章历史 +

摘要

目的：本荟萃分析是评估CD133高水平表达与肝细胞癌的临床病理及预后相关性的一个最新分析。方法：在PubMed、EMBASE、the Cochrane Library、中国CNKI和万方数据库中检索了截至2022年8月1日的CD133在肝细胞癌中的研究。使用RevMan5.3软件和Stata 13.0软件进行统计分析。结果：共确定了25项研究,涉及2700名患者。HCC患者CD133的高表达水平表明多灶性肿瘤的发生率相对较高（P=0.03）,肿瘤分化等级较低,肿瘤分期较晚,肝硬化发生率相对较高,淋巴结转移的发生率明显较高,神经侵犯的发生率明显较高,脉管癌栓的发生率明显较高。此外,CD133的表达也与总生存期和无病生存期的明显恶化有关。结论：肝细胞癌中CD133的高表达与较差的临床病理表现和较差的预后相关,为以后CD133高表达相关的上下游靶点药物的研发提供了理论支持。

Abstract

Objective This meta-analysis evaluates the correlation between CD133 expression and the clinic-pathological features and prognosis of patients with hepatocellular carcinoma. Method Until 1st February 2021, PubMed, EMBASE, the Cochrane Library, Chinese CNKI and Wan Fang databases were searched for studies of CD133 in hepatocellular carcinoma (HCC). RevMan5.3 software and Stata 13.0 software were used for statistical analyses. Results A total of 25 studies involving 2700 patients were identified. The high level of CD133 expression in HCC patients indicated a relatively higher incidence of multifocal tumor, lower tumor differentiation grade, more advanced tumor stage, a relatively higher incidence of liver cirrhosis, a significantly higher incidence of lymph node metastasis, a significantly higher incidence of neural invasion and a significantly higher incidence of lymph-vascular invasion. Additionally, CD133 expression was associated with worse overall survival (OS) and disease-free survival (DFS). Conclusion High level of CD133 expression in hepatocellular carcinoma was related with more aggressive clinical-pathological features and prognosis, suggesting another potentially feasible CD133-based targeted spot. It is necessary to focus future studies on its specific mechanism of carcinogenesis and the development of therapies that target CD133.

导出引用

张舜柏, 王志强, 张海鸿. CD133对于肝癌患者预后意义的Meta分析[J]. 湖南师范大学学报医学版. 2023, 20(2): 130-139

Zhang Shunbai, Wang Zhiqiang, Zhang Haihong. Meta-analysis of CD133 on the prognosis of patients with hepatocellular carcinoma[J]. Journal of Hunan Normal University(Medical Science). 2023, 20(2): 130-139

中图分类号： R734.2

参考文献

[1] Perz JF, Armstrong GL, Farrington LA, et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide[J]. J Hepatol, 2006, 45(4): 529-538.
[2] Omata M, Cheng AL, Kokudo N, et al. Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update[J]. Hepatol Int, 2017, 11(4): 317-370.
[3] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[4] Lau WY, Lai EC. The Current Role of Radiofrequency Ablation in the Management of Hepatocellular Carcinoma: A Systematic Review[J]. Ann Surg, 2009, 249(1): 20.
[5] Wicha MS, Liu S, Dontu G. Cancer Stem Cells: An Old Idea—A Paradigm Shift[J]. Cancer Res, 2006, 66(4): 1883-1890.
[6] Gennero L, De Siena R, Denysenko T, et al. A novel composition for in vitro and in vivo regeneration of skin and connective tissues[J]. Cell Biochem Funct, 2011, 29(4): 311-333.
[7] Todaro M, Francipane MG, Medema JP, et al. Colon cancer stem cells: promise of targeted therapy[J]. Gastroenterology, 2010, 138(6): 2151-2162.
[8] Skorzewska A, Lal S, Waserman J, et al. Abnormal food-seeking behavior after surgery for craniopharyngioma[J]. Neuropsychobiology, 1989, 21(1): 17-20.
[9] Thanan R, Pairojkul C, Pinlaor S, et al. Inflammation-related DNA damage and expression of CD133 and Oct3/4 in cholangiocarcinoma patients with poor prognosis[J]. Free Radic Biol Med, 2013, 65: 1464-1472.
[10] Park YY, An CH, Oh ST, et al. Expression of CD133 is associated with poor prognosis in stage II colorectal carcinoma[J]. Medicine (Baltimore), 2019, 98(32): e16709.
[11] Ren F, Sheng WQ, Du X. CD133: a cancer stem cells marker, is used in colorectal cancers[J]. World J Gastroenterol, 2013, 19(17): 2603-2611.
[12] Huang R, Mo D, Wu J, et al. CD133 expression correlates with clinicopathologic features and poor prognosis of colorectal cancer patients: An updated meta-analysis of 37 studies[J]. Medicine (Baltimore), 2018, 97(23): e10446.
[13] Yu GF, Lin X, Luo RC, et al. Nuclear CD133 expression predicts poor prognosis for hepatocellular carcinoma[J]. Int J Clin Exp Pathol, 2018, 11(4): 2092-2099.
[14] Song W, Li H, Tao K, et al. Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma[J]. Int J Clin Pract, 2008, 62(8): 1212-1218.
[15] Tsuchiya A, Kamimura H, Takamura M, et al. Clinicopathological analysis of CD133 and NCAM human hepatic stem/progenitor cells in damaged livers and hepatocellular carcinomas[J]. Hepatol Res, 2009, 39(11): 1080-1090.
[16] Zhong C, Wu JD, Fang MM, et al. Clinicopathological significance and prognostic value of the expression of the cancer stem cell marker CD133 in hepatocellular carcinoma: a meta-analysis[J]. Tumour Biol, 2015, 36(10): 7623-7630.
[17] Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis[J]. Trials, 2007, 8: 16.
[18] Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J]. Eur J Epidemiol, 2010, 25(9): 603-605.
[19] Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis[J]. Stat Med, 2002, 21(11): 1539-1558.
[20] Chan AW, Tong JH, Chan SL, et al. Expression of stemness markers (CD133 and EpCAM) in prognostication of hepatocellular carcinoma[J]. Histopathology, 2014, 64(7): 935-950.
[21] Chen K, Li Z H, Jiang P, et al. CD44, CD133 and TF correlate with formation of portal vein tumor thrombus and poor prognosis in patients with hepatocellular carcinoma[J]. J Third Mil Med Univ, 2014, 36: 1068-1073.
[22] Chen YL, Lin PY, Ming YZ, et al. The effects of the location of cancer stem cell marker CD133 on the prognosis of hepatocellular carcinoma patients[J]. BMC Cancer, 2017, 17: 1-9.
[23] Dai XM, Yang SL, Zheng XM, et al. CD133 expression and α-fetoprotein levels define novel prognostic subtypes of HBV-associated hepatocellular carcinoma: A long-term follow-up analysis[J]. Oncol Lett, 2018, 15(3): 2985-2991.
[24] Guo Z, Li LQ, Jiang JH, et al. Cancer stem cell markers correlate with early recurrence and survival in hepatocellular carcinoma[J]. World J Gastroenterol, 2014, 20(8): 2098.
[25] Hagiwara S, Kudo M, Ueshima K, et al. The cancer stem cell marker CD133 is a predictor of the effectiveness of S1+ pegylated interferon α-2b therapy against advanced hepatocellular carcinoma[J]. J Gastroenterol, 2011, 46: 212-221.
[26] 敬敏, 张国平, 吴欢，等. CD133与CD44蛋白在肝细胞癌组织中的表达及临床意义[J]. 西南医科大学学报, 2019, 42(05): 430-433.
[27] Jun SY, Jeon SJ, Yoon JY, et al. The positive correlation of TIPRL with LC3 and CD133 contributes to cancer aggressiveness: potential biomarkers for early liver cancer[J]. Sci Rep, 2019, 9(1): 16802.
[28] Lingala S, Cui YY, Chen X, et al. Immunohistochemical staining of cancer stem cell markers in hepatocellular carcinoma[J]. Exp Mol Pathol, 2010, 89(1): 27-35.
[29] 刘丽丽,李伟,李玉军.肝细胞癌组织CD133和CD90表达及其临床意义[J].青岛大学医学院学报,2013,49(05):393-396.
[30] 潘群雄, 苏子剑, 王聪仁, 等. 肿瘤干细胞标志EpCAM和CD133在人原发性肝癌中的表达及其对预后的临床意义[J].肿瘤, 2012, 32(08):628-633.
[31] Sasaki A, Kamiyama T, Yokoo H, et al. Cytoplasmic expression of CD133 is an important risk factor for overall survival in hepatocellular carcinoma[J]. Oncol Rep, 2010, 24(2): 537-546.
[32] 田静, 龚晓萌. CD133和maspin在肝癌中的表达及临床病理意义[J]. 中国组织化学与细胞化学杂志, 2013， 22(06): 528-532.
[33] Wu L M, Cheng C T, Chen X X, et al. Prognostic significance of expression of CD133, VEGF and CD34 in hepatocellular carcinoma[J]. Clin J Cancer Prev Treat, 2013, 20: 998-1002.
[34] Xu J, Zhang Y, Wang Y, et al. Correlation of KAI1, CD133 and vasculogenic mimicry with the prediction of metastasis and prognosis in hepatocellular carcinoma[J]. Int J Clin Exp Pathol, 2018, 11(7): 3638-3646.
[35] Xie HH, Wu W. The significance of stem cell markers CD133 and EpCAM in liver cancer tissue[J]. Int J Clin Exp Pathol, 2015, 31(05): 581-584.
[36] Yang XR, Xu Y, Yu B, et al. High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma[J]. Gut, 2010, 59(7): 953-962.
[37] Ye F, Jing YY, Guo SW, et al. Proliferative ductular reactions correlate with hepatic progenitor cell and predict recurrence in HCC patients after curative resection[J]. Cell Biosci, 2014, 4(1): 1-14.
[38] Yeh CT, Kuo CJ, Lai MW, et al. CD133-positive hepatocellular carcinoma in an area endemic for hepatitis B virus infection[J]. BMC Cancer, 2009, 9(1): 1-11.
[39] Yilmaz G, Akyol G, Cakir A, et al. Investigation of diagnostic utility and expression profiles of stem cell markers (CD133 and CD90) in hepatocellular carcinoma, small cell dysplasia, and cirrhosis[J]. Pathol Res Pract, 2014, 210(7): 419-425.
[40] Zen C, Zen Y, Mitry RR, et al. Mixed phenotype hepatocellular carcinoma after transarterial chemoembolization and liver transplantation[J]. Liver Transpl, 2011, 17(8): 943-954.
[41] 曾宪成,张彤,傅斌生等.肿瘤干细胞表面标志物CD133在肝细胞肝癌组织中的表达及其与肝移植患者预后的关系[J].中华肝脏外科手术学电子杂志, 2012, 1(01):51-56.
[42] Chiba T, Zheng YW, Kita K, et al. Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation[J]. Gastroenterology, 2007, 133(3): 937-950.
[43] Nguyen LV, Vanner R, Dirks P, et al. Cancer stem cells: an evolving concept[J]. Nat Rev Cancer, 2012, 12(2): 133-143.
[44] Miraglia S, Godfrey W, Yin AH, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning[J]. Blood, 1997, 90(12): 5013-5021.
[45] Kuçi S, Wessels JT, Bühring HJ, et al. Identification of a novel class of human adherent CD34- stem cells that give rise to SCID-repopulating cells[J]. Blood, 2003, 101(3): 869-876.
[46] Tang KH, Ma S, Lee TK, et al. CD133+ liver tumor-initiating cells promote tumor angiogenesis, growth, and self-renewal through neurotensin/interleukin-8/CXCL1 signaling[J]. Hepatology, 2012, 55(3): 807-820.
[47] Kim H, Choi GH, Na DC, et al. Human hepatocellular carcinomas with “Stemness”-related marker expression: keratin 19 expression and a poor prognosis[J]. Hepatology, 2011, 54(5): 1707-1717.
[48] Attia S, Atwan N, Arafa M, et al. Expression of CD133 as a cancer stem cell marker in invasive gastric carcinoma[J]. Pathologica, 2019, 111(1): 18.
[49] Song S, Pei G, Du Y, et al. Interaction between CD133 and PI3K-p85 promotes chemoresistance in gastric cancer cells[J]. Am J Transl Res, 2018, 10(1): 304.
[50] Li N, Dai C, Yang Y, et al. The expression levels and clinical significance of MFG-E8 and CD133 in epithelial ovarian cancer[J]. Gynecol Endocrinol, 2020, 36(9): 803-807.
[51] Gzil A, Zarębska I, Bursiewicz W, et al. Markers of pancreatic cancer stem cells and their clinical and therapeutic implications[J]. Mol Biol Rep, 2019, 46: 6629-6645.
[52] Röper K, Corbeil D, Huttner WB. Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane[J]. Nat Cell Biol, 2000, 2(9): 582-592.
[53] Mizukami T, Kamachi H, Mitsuhashi T, et al. Cytoplasmic CD133 expression correlates with histologic differentiation and is a significant prognostic factor in extrahepatic bile duct cancer and gallbladder cancer[J]. Oncol Lett, 2018, 16(5): 6423-6430.
[54] Fan L, He F, Liu H, et al. CD133: a potential indicator for differentiation and prognosis of human cholangiocarcinoma[J]. BMC Cancer, 2011, 11: 1-8.
[55] Fabris L, Cadamuro M, Moserle L, et al. Nuclear expression of S100A4 calcium-binding protein increases cholangiocarcinoma invasiveness and metastasization[J]. Hepatology, 2011, 54(3): 890-899.
[56] Chu X, Zhao P, Lv Y, et al. Decreased expression of TFPI-2 correlated with increased expression of CD133 in cholangiocarcinoma[J]. Int J Clin Exp Pathol, 2015, 8(1): 328.
[57] Cai X, Li J, Yuan X, et al. CD133 expression in cancer cells predicts poor prognosis of non-mucin producing intrahepatic cholangiocarcinoma[J]. J Transl Med, 2018, 16(1): 1-7.
[58] Bussolati B, Moggio A, Collino F, et al. Hypoxia modulates the undifferentiated phenotype of human renal inner medullary CD133+ progenitors through Oct4/miR-145 balance[J]. Am J Physiol Renal Physiol, 2012, 302(1): F116-F128.
[50] Griguer CE, Oliva CR, Gobin E, et al. CD133 is a marker of bioenergetic stress in human glioma[J]. PLoS One, 2008, 3(11): e3655.
[60] Dubrovska A, Kim S, Salamone RJ, et al. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations[J]. Proc Natl Acad Sci U S A, 2009, 106(1): 268-273.
[61] 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.