Significance of CD44 expression in head and neck cancer: a systemic review and meta-analysis

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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 head and neck squamous cell cancer (HNSCC). However, the prognostic value of CD44 still remains controversial; hence, we investigated the correlation between CD44 and the clinicopathological features of HNSCC by meta-analysis.

Methods

A comprehensive search was performed using PubMed, ISI web of Science and China National Knowledge Infrastructure (CNKI) up to April 2013. Only studies with immunohistochemical staining of HNSCC were considered. Data on TNM classification, tumor grade, disease free survival and 3- or 5-year overall survival rate were extracted.

Results

Thirty studies with 2102 patients met the inclusion criteria for the meta-analysis. Fifteen studies used anti-pan-CD44 antibody, 9 used anti-CD44-v6 antibody, 2 used anti-CD44-v3 and 2 used anti-CD44s antibody, 1 used anti-CD44-v9, and 1 used anti-CD44-v6,-v3 and -v4-5 simultaneously. The total percentage of CD44 expression was 57.8%, with 49.3% in oral cancer patients, 66.4% in pharynx and 54.7% in larynx cancer patients expressing CD44. No significant correlation between clinical features and CD44 expression was revealed for oral cancer patients, but CD44 was shown to be associated with advanced T categories (larynx: RR = 1.33, 95% CI 1.01-1.76; larynx & pharynx RR = 1.21, 95% CI 1.08-1.35), worse N categories (larynx: RR = 2.53, 95% CI 1.99-3.21; larynx & pharynx RR = 1.95, 95% CI 1.35-2.82), higher tumor grades (larynx & pharynx RR = 1.71, 95% CI 1.04-2.79) and 5-year OS rates (larynx: RR = 0.62, 95% CI 0.47-0.83; larynx & pharynx RR = 0.66, 95% CI 0.47-0.94) in patients with laryngeal and pharyngolaryngeal cancer. In stratified analysis, pan-CD44 and CD44-v6 expression were both correlated with 5-year OS rate of patients with laryngeal (CD44: RR = 0.66, 95% CI 0.46-0.95; CD44-v6 RR = 0.53, 95% CI 0.37-0.77) and pharyngolaryngeal cancer (CD44: RR = 0.56, 95% CI 0.34-0.93; CD44-v6 RR = 0.53, 95% CI 0.37-0.77).

Conclusions

Our analysis suggested that CD44 is related to worse T category, N category, tumor grade and prognosis, in pharyngeal and laryngeal cancer, but no clear association was revealed between CD44 expression and oral cancer.

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Most cited references 45

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Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma.

Shih-Hwa Chiou, Cheng-Chia Yu, Chi-Yang Huang … (2008)

Oral squamous cell carcinoma (OSCC), like many solid tumors, contains a heterogeneous population of cancer cells. Recent data suggest that a rare subpopulation of cancer cells, termed cancer stem cells (CSC), is capable of initiating, maintaining, and expanding the growth of tumor. Identification and characterization of CSC from OSCC facilitates the monitoring, therapy, or prevention of OSCC. We enriched oral cancer stem-like cells (OC-SLC) through sphere formation by cultivating OSCC cells from established OSCC cell lines or primary cultures of OSCC patients within defined serum-free medium. Differential expression profile of stemness genes between enriched OC-SLC and parental OSCC was elucidated. Furthermore, immunohistochemical staining of stemness markers on OSCC patient tissues was examined to evaluate the association between stemness genes and prognosis of OSCC. Enriched OC-SLC highly expressed the stem/progenitor cell markers and ABC transporter gene (Oct-4, Nanog, CD117, Nestin, CD133, and ABCG2) and also displayed induced differentiation abilities and enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Elevated expression of CD133 was shown in the enriched OC-SLC from OSCC patients' tumors. Positive correlations of Oct-4, Nanog, or CD133 expression on tumor stage were shown on 52 OSCC patient tissues. Kaplan-Meier analyses exhibited that Nanog/Oct-4/CD133 triple-positive patients predicted the worst survival prognosis of OSCC patients. We enriched a subpopulation of cancer stem-like cell from OSCC by sphere formation. The enriched OC-SLC possesses the characteristics of both stem cells and malignant tumors. Additionally, expression of stemness markers (Nanog/Oct-4/CD133) contradicts the survival prognosis of OSCC patients.

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CD44, a therapeutic target for metastasising tumours.

Véronique Orian-Rousseau (2010)

Members of the CD44 family of transmembrane glycoproteins, in particular CD44v6 isoforms, were shown to be metastatic determinants of rat pancreatic tumour cells back in the early 1990s. Furthermore, the expression of several CD44 proteins correlates with aggressive stages of various human cancers. Because of the frequent and homogeneous expression of CD44v6 isoforms in squamous cell carcinoma, antibodies recognising these proteins were used in clinical trials for patients suffering from head and neck squamous cell carcinoma (HNSCC). Although the phase I clinical trials looked promising, the studies were abruptly ended after the death of a patient. Despite the termination of the trials, CD44 certainly remains a valid target for anti-cancer therapy. In this review, alternative strategies targeting CD44 functions are presented. These functions include the binding to hyaluronan (HA), the collaboration with osteopontin and the contribution of CD44 isoforms to receptor tyrosine kinase (RTKs) activation. These new attempts led to the development of peptides that interfere for example with HA binding and that might be used to induce apoptosis in mammary carcinoma or to prevent homing of leukaemia stem cells. Other peptides block RTK activation and thereby inhibit tumour angiogenesis and metastatic spread. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis.

Olivier Poch, Frédéric Lemaire, Julia Young … (2004)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer among men in the developed world. There is a need, for both clinical and scientific reasons, to find markers to identify patients with aggressive disease as early as possible, and to understand the events leading to malignant transformation and susceptibility to metastasis. We report the first large-scale gene expression analysis of a unique HNSCC location, the hypopharynx. Four normal and 34 tumour samples were analysed with 12 600 gene microarrays. Clusters of differentially expressed genes were identified in the chromosomal regions 3q27.3, 17q21.2-q21.31, 7q11.22-q22.1 and 11q13.1-q13.3, which, interestingly, have already been identified by comparative genomic hybridization (CGH) as major regions of gene amplification. We showed that six overexpressed genes (EIF4G1, DVL3, EPHB4, MCM7, BRMS1 and SART1) located in these regions are indeed amplified. We report 119 genes that are highly differentially expressed between 'early' tumours and normal samples. Of these, we validated by quantitative PCR six novel poorly characterized genes. These genes are potential new markers of HNSCC. Comparing patients with relatively nonaggressive and aggressive tumours (without or with clinical evidence of metastasis 3 years after surgery), we identified 164 differentially expressed genes potentially involved in the acquisition of metastatic potential. This study contributes to the understanding of HNSCC, staging patients into prognostic groups and identifying high-risk patients who may benefit from more aggressive treatment.

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Author and article information

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central

ISSN (Electronic): 1471-2407

Publication date Collection: 2014

Publication date (Electronic): 13 January 2014

Volume: 14

Page: 15

Affiliations

[1 ]Department of Otorhinolaryngology, Affiliated Cixi Hospital of Wenzhou Medical, College, Cixi 315300, China

Article

Publisher ID: 1471-2407-14-15

DOI: 10.1186/1471-2407-14-15

PMC ID: 3893437

PubMed ID: 24410905

SO-VID: 9235ea43-79dd-4035-ac7d-d4143bf61d31

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Significance of CD44 expression in head and neck cancer: a systemic review and meta-analysis

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Abstract

Background

Methods

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Conclusions

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Karger: Oncology

Most cited references 45

Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma.

CD44, a therapeutic target for metastasising tumours.

Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis.

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