Expression of the receptor for advanced glycation end-products and frequency of polymorphism in lung cancer

Abstract

Abstract. Receptor for advanced glycation end products (RAGE) is associated with the pathogenesis of cancer progression. The pathological effects mediated through RAGE are physiologically inhibited by soluble RAGE (sRAGE). The aim of the present study was to identify the expression of the sRAGE, RAGE and RAGE ligands in serum samples and lung cancer tissue obtained from lung cancer patients. Using ELISA and immunohistochemistry, it was observed that the sRAGE levels were downregulated in the serum, the expression of RAGE was decreased in the lung cancer tissue and the RAGE ligands HMGB1 and S100 were upregulated in cancer tissue. Furthermore, the presence of several selected types of RAGE polymorphism that occur in lung cancers were measured in the tissue samples. An association between the -429T/C and 2184A/G polymorphisms of RAGE and the genesis and progression of lung cancer was identified. The comparison between various histological subtypes and stages of lung cancer was performed with the aim to clarify the biological role of the RAGE gene, and identify a biomarker to aid diagnosis and predict the prognosis for lung cancer patients.

All the “RAGE” in lung disease: The receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses

“…Moreover, it has been demonstrated that over-expression of RAGE in lung cancer cells reduces proliferation and tumor growth [28,122]. Paradoxically, although RAGE is decreased in lung cancer, its ligands, which are often associated with proliferative effects, are increased [123–126] and are predictors of poor prognosis [127]. This may be due in part to the fact that the predominant cell-type in lung cancers is the bronchial epithelial cell, which does not typically express RAGE.…”

The role of high‐mobility group protein box 1 in lung cancer

“…Although the role of HMGB1 in NSCLC is a research hotspot in recent years, the underlying molecular mechanisms for the HMGB1‐mediated progression, metas­tasis, and autophagy of lung cancer have not yet been fully elucidated. Many studies demonstrated that the combination of HMGB1 and RAGE was closely associated with the development of lung cancer . Normal human bronchial epithelial cells (NHBE) have the potency with NSCLC initiation in inflammatory microenvironment .…”

Lung adenocarcinoma expressing receptor for advanced glycation end-products with primary systemic AL amyloidosis: a case report and literature review

“…RAGE and its ligands are highly upregulated in cancer tissue (e.g., pancreatic, colon, and prostate cancer) [7]. By contrast, both RAGE and serum soluble RAGE (sRAGE) levels are downregulated in smokers and lung cancer patients [7–9]. …”

“…We were not able to monitor the clinical time course of serum sRAGE level as a surrogate marker in this case. There is speculation that downregulation of both RAGE and sRAGE may be a critical step in the formation of lung tumours [8, 9, 14]. Several genetic single nucleotide polymorphism (SNP) studies identified that the SNPs in the RAGE associated with increased NSCLC risk and a lower chemotherapy response rate and poor prognosis [9, 15, 16].…”

“…There is speculation that downregulation of both RAGE and sRAGE may be a critical step in the formation of lung tumours [8, 9, 14]. Several genetic single nucleotide polymorphism (SNP) studies identified that the SNPs in the RAGE associated with increased NSCLC risk and a lower chemotherapy response rate and poor prognosis [9, 15, 16]. In addition, increasing concentrations of SAA corresponded to poor response to tyrosine kinase inhibitors and correlated with poor clinical outcome [2, 17].…”