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Tumor Discovery RAGEs in oral squamous cell carcinoma

of advanced glycation end products (AGEs). It has been subjected to a systematic review, and the results were
demonstrated that the presence of AGEs increases cellular tabulated and analyzed in Table 1.
dysfunction, vascular alteration, apoptosis, and activation
of inflammatory pathways. Receptors of advanced glycation 3. Results
end products (RAGEs) are a receptor for several ligands, About 28% of the articles utilizing immunohistochemistry
including amphoterin, advanced glycation products, (IHC) demonstrated that RAGE products are more
b-amyloids, and S100 proteins [3,4] . prevalent in the invasive front of tumor tissues, and 43%

The gene for RAGE is located on chromosome 6p21.3 of the articles demonstrated that high expression of these
at the class II/III junction of the major histocompatibility receptors increased the motility of tumor cells. Due to
complex and has a 1.7 kb 5’ flanking region, 11 exons, 10 their compatibility with several ligands, these receptors
introns, and a 3’ untranslated region [5,6] . RAGE products are are crucial for tumor cell angiogenesis, invasiveness, and
raised in a variety of clinical conditions, including several metastasis, making RAGEs an essential biomarker for
cancers. At each stage of the lesion, RAGE is expressed determining the prognosis of oral carcinomas.
in the tissue in a distinct manner. The RAGE, commonly 4. Discussion
referred to as a “pattern recognition receptor,” is a member
of the immunoglobulin superfamily of cell surface RAGE is a cell surface receptor belonging to the
[7]
molecules with a diverse array of ligand specificities . immunoglobulin superfamily. They display molecule types
produced by the non-enzymatic glycation of proteins
By interacting with its varied ligand families, RAGE
orchestrates several intracellular signaling pathways through Millard’s reaction. RAGE is expressed at low levels
in normal tissue and vasculature during development. It
to govern numerous cellular functions, including appears uncontrolled wherever its ligands congregate
[9]
inflammation, apoptosis, proliferation, and autophagy. and is elevated in numerous clinical and non-pathological
In animal models, it has also been demonstrated that situations. The pro-inflammatory RAGE ligand high
inhibiting RAGE signaling inhibits cancer growth and motility group box 1 (HMGB-1) is frequently released by
metastasis through regulating tumor proliferation, necrotic cells. HMGB-1 and RAGE have also been reported
invasion, and matrix metalloproteinase expression . to interact in chronic inflammation and the immune system.
[8]
The purpose of this literature review is to establish the The average RAGE concentration in cancer samples was 57
relationship between RAGEs and OSCC by clarifying ± 1.9 pg/mL. In a study, Sasahira et al. hypothesized that
the importance of RAGE as a diagnostic and predictive the concentration of RAGE declines with the progression
biomarker for oral malignancies as well as a potential of cancer; this is due to the consumption of such molecules
treatment strategy. during the process of cancer initiation, and the emergence of
[10]
2. Materials and methods numerous other components in the later stages of cancer .
Consequently, the concentration of these receptors may be
We conducted a comprehensive search in PubMed, depleted during the later stages of cancer .
[11]
Google, and Cochrane for publications published up to
December 2017 that explored the connection between In seven studies encompassing 820 cases and 626
RAGE and oral cancer. Several crucial terminologies were controls, the overall RAGE levels were shown to be higher
in well-differentiated OSCC and lower as differentiation
used separately and in conjunction: RAGE, receptor for decreased in this systematic review.
advanced glycation end products, or AGE, oral cancer,
carcinoma, oral neoplasm, and squamous cell carcinoma. Due to its potential to alter the HMGB-1, it is evident
that RAGE has a strong relationship with cell motility; this
Exclusion criteria included non-English publications,
conference abstracts, and studies that did not involve has been demonstrated in 43% of the publications, hence
boosting the invasiveness of the tumor. Using the Boyden
human subjects or samples, reviews, and articles relating to Chamber experiment, Choi et al. demonstrated that RAGE,
other head and neck tumors, and studies assessing the effect in conjunction with HMGB-1, considerably increases the
of drug therapy. Articles on oral cancer, cross-sectional motility of the cells, while Ujjal et al. demonstrated that
research, and RAGE values are included as inclusion antisense RAGE inhibits this motility. In their study, Shun
criteria. Following a review of article titles and abstracts, et al. demonstrated that RAGE antibodies inhibit cell
seven full-text studies were retrieved for inclusion in the motility, underscoring the importance of these receptors
study.
in the enhanced cell motility observed in cases of OSCC.
Due to the heterogeneity of the analyzed studies, a The antibody against RAGE may inhibit the motility and
meta-analysis was not possible. The collected papers were migration of cells, thereby facilitating targeted therapy.

Volume 2 Issue 1 (2023) 2 https://doi.org/10.36922/td.244