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

Abstract

BackgroundCD44 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.MethodsA 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.ResultsThirty 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).ConclusionsOur 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.

Human salivary proteome — a resource of potential biomarkers for oral cancer

“…CD44, tenascin C (TNC) and cysteine rich transmembrane BMP regulator 1 (CRIM1) are some of the important molecules representing cell communication and signal transduction process. CD44 has been reported to be involved with tumor growth and metastasis and has also been implicated as a cancer stem cell marker in head and neck squamous cell cancer (HNSCC) and is also associated with bad prognosis [44]. TNC is an extracellular matrix protein with growth, invasion and angiogenesis-promoting activities.…”

Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma

“…For example, CD133 (prominin-1), an apical plasma membrane protein predominantly on embryonic epithelial structures, has been reported to be an important CSC marker in a number of solid malignancies, including brain tumor [10], prostate carcinoma [11], ovarian carcinoma [12], colorectal cancer [13], osteosarcoma [14] and lung cancer [15]. Besides breast cancer, CD44 is also involved in the tumorigenic CSCs of colon cancer, ovarian carcinoma, head and neck squamous cell carcinoma [16] and prostate cancer. In liver cancer, the sickness generally develops in the setting of chronic liver disease, in which continuous inflammation and hepatocyte regeneration occur.…”

Head and Neck Cancer Stem Cells

“…First, while FACS analysis is a robust tool to identify cancer stem cells, extrinsic factors (e.g., machine calibration, use of proper controls, and compensation/ gating protocols) and intrinsic factors (e.g., cell confluency, specific splice variants/isoforms, and clonal variations) can significantly affect the accuracy and reproducibility of results. Second, in the context of cell surface antigens, expression does not necessarily correspond to cancer stem cell behavior or clinical manifestation, as was shown in CD44+ cells in HNSCC (Chen et al 2014). Finally, stemlike characteristics in cancer cells can be lost or regained depending on interactions with tumor stroma (Chaffer et al 2011).…”