Oncotarget. 2017 Nov 10; 8(56): 96359–96372.
Published online 2017 Jul 27. doi: 10.18632/oncotarget.19648
PMCID: PMC5707106
PMID: 29221212
Prognostic and clinicopathological significance of MUC expression in head and neck cancer: a systematic review and meta-analysis
This article has been cited by other articles in PMC.
Abstract
The
prognostic value of mucins expression in patients with head and neck
cancer (HNC) remains controversial. To address this, a meta-analysis was
performed to systematically evaluate prognostic significance of mucins
expression in HNC. Electronic and manual searches were performed and a
total of 20 studies including 2046 patients were selected for the final
analysis. Increased mucins expression was associated with unfavorable
overall survival in HNC patients (HR=1.83, 95% CI: 1.43-2.33, p=0.000). Mucins overexpression was also in correlation with more advanced TNM stage (RR=0.84, 95% CI: 0.73-0.97, p=0.017), higher risk of lymph node metastasis (RR=0.69, 95% CI: 0.57-0.84, p=0.000) and deeper invasion (RR=0.58, 95% CI: 0.44-0.76, p=0.000).
These results suggested that elevated mucins expression was
significantly associated with worse prognosis and more detrimental
clinicopathological outcomes, revealing the promising potential of
mucins as biomarkers for HNC management.
Keywords: MUC, head and neck cancer, biomarkers, prognosis, meta-analysis
INTRODUCTION
Head
and neck cancer (HNC) is a group of biologically similar cancers
originating from the oral cavity, nasopharyngeal, oropharynx,
hypopharynx and larynx, which mainly behave as squamous cell carcinoma
histologically. HNC is the sixth most frequent type of malignant tumor,
causing more than 400,000 deaths annually worldwide [1-5].
Its high mortality rate and the disfigurement or functional deficiency
that survivors may suffer result in a considerable global public health
burden. Despite great advance in multidisciplinary combined diagnosis
and treatment, only 30-50% patients with HNC survive over 5 years after
initial diagnosis worldwide [6].
Clinically, the classic tumor, node, and metastasis (TNM) staging
system is widely used for the initial diagnosis but failed to reflect
the inherent biological heterogeneity especially in atypical early
symptoms or concealed metastasis patients. Therefore, novel biomarkers
involved in cancer development are greatly needed to stratify patients
with poor prognosis of HNC in order to make optimal individualized
therapy.
Much attention has been focused on the
involvement of mucins (MUC) in tumor carcinogenesis and metastasis
recently. MUC is a family of high O-glycosylated protein, characterized
by a basic structure including a central polymorphic tandem repeat
region [7-8].
Only expressing on the apical surfaces of various luminal and glandular
normal epithelial cells, MUC play an important role in cell-cell
adhesion, immune response and alteration of intracellular signaling [9].
However, the tightly regulated homeostatic expression may be disrupted
by various factors such as cancer cells, in particular. The observation
of subcellular distribution and biochemical features changes during
malignant transformation and tumor progression suggest that MUC may be
the key point in carcinogenesis and subsequent metastasis of cancers [10-14]. Therefore, aberrant MUC expression may be predictive biomarkers in HNC.
Over
the past decade, numerous independent studies have evaluated the
clinical and the prognostic value of MUC protein expression in HNC. Yet,
the results of these reports remain controversial and no clear
consensus has been achieved so far [15-19].
Limited to small sample size some publications may draw inconsistent
results due to potential random errors. Therefore, we conducted a
systematic review and meta-analysis to address the association between
MUC expression and prognostic value and the common clinicopathological
parameters of HNC.
Comment
Results from this hospital-based, case-control study
support the hypothesis that aspirin use is associated with reduced risk
of HNC. A plausible explanation is that aspirin, a nonselective
cyclooxygenase (COX) inhibitor, blocks the action of COX-1 and COX-2, in
turn inhibiting prostaglandin (PG) synthesis, particularly PGE2.10 Expression of COX-2 and PGE2
in tumors has been proved to be associated with suppressed immune
response, enhanced inflammation, increased angiogenesis, augmented
cellular proliferation, and inhibited apoptotic pathway, thereby
promoting tumor progression and invasion.5
This theory is further supported by studies that demonstrate an
increased level of COX expression in various other malignant lesions.11,12 Numerous laboratory investigations have also revealed up-regulated COX-2 and PGE2 expression in premalignant and malignant head and neck lesions.13,14
Immunohistochemical analyses have also shown a gradient increase in
expression of COX-2 depending on the grade of the oral mucosal lesion,
from hyperplasia to dysplasia, with the highest expression in SCC.15 In addition, administration of aspirin and other NSAIDs has been shown to inhibit HNC in animal models.16,17
Abstract
Inga kommentarer:
Skicka en kommentar