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Cancer Cell International
Published in: Cancer Cell International 1/2016

Open Access 01-12-2016 | Primary research

Prognostic value of CD44 expression in patients with hepatocellular carcinoma: meta-analysis

Authors: Yangkun Luo, Yan Tan

Published in: Cancer Cell International | Issue 1/2016

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Abstract

Background

CD44 has been reported to be involved with tumor growth and metastasis and has also been implicated as a CSC marker in hepatocellular carcinoma (HCC). However, the prognostic value of CD44 still remains controversial; hence, we investigated the correlation between CD44 and the clinicopathological features of HCC by meta-analysis.

Methods

Identification and review of publications assessing clinical or prognostic significance of CD44 expression in HCC until November 1, 2015. A meta-analysis was performed to clarify the association between CD44 expression and clinical outcomes.

Results

A total of 14 publications met the criteria and comprised 2235 cases. Analysis of these data showed that CD44 expression was not significantly associated with the tumor differentiation (OR 1.48, 95 % confidence interval [CI] 0.85–2.60, P = 0.17), AFP level of HCC patients (OR 0.83, 95 % CI 0.52–1.33, P = 0.45), or disease-free survival (relative risk [RR] 1.15, 95 % CI, 0.85–1.54; P = 0.36). However, in the identified studies, CD44 expression was highly correlated with tumor TNM classification (OR 2.38, 95 % CI 1.23–4.60; P = 0.01) and decreased overall survival (RR 1.49, 95 % CI, 1.26–1.76; P < 0.00001).

Conclusions

This meta-analysis shows CD44 expression in HCC is connected with decreased overall and thus marks a worse prognosis.
Literature
1.
Ormandy LA, Hillemann T, Wedemeyer H, Manns MP, Greten TF, Korangy F. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res. 2005;65(6):2457–64.CrossRefPubMed
2.
Lee J-S, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, Mikaelyan A, Roberts LR, Demetris AJ, Sun Z, Nevens F, Roskams T, Thorgeirsson SS. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med. 2006;12(4):410–6.CrossRefPubMed
3.
Malanchi I, Santamaria-Martínez A, Susanto E, Peng H, Lehr HA, Delaloye JF, Huelsken J. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature. 2012;481(7379):85–9.CrossRef
4.
5.
Ma S. Biology and clinical implications of CD133 + liver cancer stem cells. Exp Cell Res. 2013;319(2):126–32.CrossRefPubMed
6.
Okabe H, Ishimoto T, Mima K, Nakagawa S, Hayashi H, Kuroki H, Imai K, Nitta H, Saito S, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Nagano O, Beppu T, Saya H, Baba H. CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma. Br J Cancer. 2014;110(4):958–66.CrossRefPubMed
7.
Sakamoto T, Hara M, Higaki Y, Ichiba M, Horita M, Mizuta T, Eguchi Y, Yasutake T, Ozaki I, Yamamoto K, Onohara S, Kawazoe S, Shigematsu H, Koizumi S, Tanaka K. Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population. Int J Cancer. 2006;118(6):1501–7.CrossRefPubMed
8.
9.
Wei KC, Huang CY, Chen PY, Feng LY, Wu TW, Chen SM, Tsai HC, Lu YJ, Tsang NM, Tseng CK, Pai PC, Shin JW. Evaluation of the prognostic value of CD44 in glioblastoma multiforme. Anticancer Res. 2010;30(1):253–9.PubMed
10.
Li Z, Chen K, Jiang P, Zhang X, Li X, Li Z. CD44v/CD44s expression patterns are associated with the survival of pancreatic carcinoma patients. Diagn Pathol. 2014;9(79):1186.
11.
van der Windt GJ, Schouten M, Zeerleder S, Florquin S, van der Poll T. CD44 is protective during hyperoxia-induced lung injury. Am J Respir Cell Mol Biol. 2011;44(3):377–83.CrossRefPubMed
12.
Negi LM, Talegaonkar S, Jaggi M, Ahmad FJ, Iqbal Z, Khar RK. Role of CD44 in tumour progression and strategies for targeting. J Drug Target. 2012;20(7):561–73.CrossRefPubMed
13.
Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990;61(7):1303–13.CrossRefPubMed
14.
Orian-Rousseau V. CD44, a therapeutic target for metastasising tumours. Eur J Cancer. 2010;46(7):1271–7.CrossRefPubMed
15.
Wibulswas A, Croft D, Pitsillides AA, Bacarese-Hamilton I, McIntyre P, Genot E, Kramer IM. Influence of epitopes CD44v3 and CD44v6 in the invasive behavior of fibroblast-like synoviocytes derived from rheumatoid arthritic joints. Arthritis Rheum. 2002;46(8):2059–64.CrossRefPubMed
16.
Mima K, Okabe H, Ishimoto T, Hayashi H, Nakagawa S, Kuroki H, Miyake K, Takamori H, Beppu T, Baba H. The expression levels of CD44v6 are correlated with the invasiveness of hepatocellular carcinoma in vitro, but do not appear to be clinically significant. Oncol Lett. 2012;3(5):1047–51.PubMedPubMedCentral
17.
Ryu HS, Park SH, Lee KB, Shin E, Jang J-J. Expression of the transmembrane glycoprotein cd44s is potentially an independent predictor of recurrence in hepatocellular carcinoma. Gut Liver. 2011;5(2):204–9.CrossRefPubMedPubMedCentral
18.
Endo K, Terada T. Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, p53 expression, and patient survival. J Hepatol. 2000;32(1):78–84.CrossRefPubMed
19.
Mima K, Okabe H, Ishimoto T, Hayashi H, Nakagawa S, Kuroki H, Watanabe M, Beppu T, Tamada M, Nagano O, Saya H, Baba H. CD44s Regulates the TGF-β–mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res. 2012;72(13):3414–23.CrossRefPubMed
20.
Hu S, Wu X, Zhou B, Xu Z, Qin J, Lu H, Lv L, Gao Y, Deng L, Yin J, Li G. IMP3 combined with CD44s, a novel predictor for prognosis of patients with hepatocellular carcinoma. J Cancer Res Clin Oncol. 2014;140(6):883–93.CrossRefPubMed
21.
Zhang KL, Wang ZM, Wei SD. Significance of CD44v6 and c-Met expression in hepatocellular carcinoma. Chin J Gener Surg. 2008;17(1):94–7.
22.
Huang KH, Yuan SZ. Study of significance of CD44v6 expression in hepatocellular carcinoma. Chin J Cancer. 2001;20(2):200–1.
23.
Peng H, Yang HW, Song LW, Zhou Z. The expression and significance of PCNA and CD44v6 in hepatocellular carcinoma. Shandong Med. 2010;50(32):45–6.
24.
Zhou ZJ, Dai Z, Zhou SL, Fu XT, Zhao YM, Shi YH, Zhou J, Fan J. Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma. Int J Cancer. 2013;132(5):1080–9.CrossRefPubMed
25.
Tovuu L-O, Imura S, Utsunomiya T, Morine Y, Ikemoto T, Arakawa Y, Mori H, Hanaoka J, Kanamoto M, Sugimoto K, Iwahashi S, Saito Y, Yamada S, Asanoma M, Miyake H, Shimada M. Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma. Int J Clin Oncol. 2013;18(4):651–6.CrossRefPubMed
26.
Chen K, Li ZH, Jiang P, Zhang X, Zhang YJ, Jiang YJ, Li XW. CD44, CD133 and TF correlate with formation of portal vein tumor thrombus and poor prognosis in patients with hepatocellular carcinoma. J Third Mil Med Univ. 2014;10:022.
27.
Su JG, Zhu SL, Xiao JC, Wang TX, Xiang M. Expression of CD44 in hepatocellular carcinoma and adjacent tissues and Its significances. Cancer Res Clin. 2006;18(9):612–4.
28.
Yang G-H, Fan J, Xu Y, Qiu SJ, Yang XR, Shi GM, Wu B, Dai Z, Liu YK, Tang ZY, Zhou J. Osteopontin combined with CD44, a novel prognostic biomarker for patients with hepatocellular carcinoma undergoing curative resection. Oncologist. 2008;13(11):1155–65.CrossRefPubMed
29.
Cao Z. The expression of cancer stem cell markers (CD133, CD90, CD44, ALDH1) relates to the prognosis and metabolic index in patients with hepatocellular carcinoma. Anhui medical university. 2008.
30.
Hagiwara S, Kudo M, Ueshima K, Chung H, Yamaguchi M, Takita M, Haji S, Kimura M, Arao T, Nishio K, Park AM, Munakata H. The cancer stem cell marker CD133 is a predictor of the effectiveness of S1 + pegylated interferon α-2b therapy against advanced hepatocellular carcinoma. J Gastroenterol. 2011;46(2):212–21.CrossRefPubMed
31.
Chan AW, Tong JH, Chan SL, Lai P, To KF. Expression of stemness markers (CD133 and EpCAM) in prognostication of hepatocellular carcinoma. Histopathology. 2014;64(7):935–50.CrossRefPubMed
32.
Wong E, Srivastava S, Yeoh KG, Teh M, Salto-Tellez M. Clinical and biological relevance of Thy-1/CD90 protein overexpression in human hepatocellular carcinoma. J Onco Pathol. 2013;1(2):1–9.
33.
Du L, Wang H, He L, Zhang J, Ni B, Wang X, Jin H, Cahuzac N, Mehrpour M, Lu Y, Chen Q. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res. 2008;14(21):6751–60.CrossRefPubMed
34.
Wielenga VJ, Heider K-H, Johan G, et al. Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res. 1993;53(20):4754–6.PubMed
35.
Lafleur L, Johansson AC, Roberg K. A CD44 high/EGFR low subpopulation within head and neck cancer cell lines shows an epithelial-mesenchymal transition phenotype and resistance to treatment. PloS ONE. 2012;7:e44071.CrossRef
36.
Wang SJ, Wong G, de Heer AM, Xia W, Bourguignon LY. CD44 variant isoforms in head and neck squamous cell carcinoma progression. Laryngoscope. 2009;119(8):1518–30.CrossRefPubMedPubMedCentral
37.
Ni J, Cozzi PJ, Hao JL. CD44 variant 6 is associated with prostate cancer metastasis and chemo-/radioresistance[J]. Prostate. 2014;74(6):602–17.CrossRefPubMed
38.
Horiguchi K, Toi M, Horiguchi S, Sugimoto M, Naito Y, Hayashi Y, Ueno T, Ohno S, Funata N, Kuroi K, Tomita M, Eishi Y. Predictive value of CD24 and CD44 for neoadjuvant chemotherapy response and prognosis in primary breast cancer patients. J Med Dent Sci. 2010;57(2):165–75.PubMed
39.
Liang Y-M, Li X-H, Li W-M, Lu Y-Y. Prognostic significance of PTEN, Ki-67 and CD44 s expression patterns in gastrointestinal stromal tumors. World J Gastroenterol WJG. 2012;18(14):1664.CrossRefPubMed
40.
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8(1):16.CrossRefPubMedPubMedCentral
Metadata
Title
Prognostic value of CD44 expression in patients with hepatocellular carcinoma: meta-analysis
Authors
Yangkun Luo
Yan Tan
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2016
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-016-0325-2

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