Endogenous secretory receptor for advanced glycation end products in non-small cell lung carcinoma
Seiichi Kobayashi1, Hiroshi Kubo, Takashi Suzuki
1Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryoumachi, Aobaku, Sendai, Japan.
Rationale:
The receptor for advanced glycation end products is a multiligand receptor that plays an important role in regulating the invasiveness and metastatic potential of cancer cells. A recently discovered novel splice variant, the endogenous secretory receptor for advanced glycation end products, mediates the receptor for advanced glycation end-product-associated cell responses by functioning as a decoy receptor.
Objectives:
To evaluate the expression pattern of endogenous secretory receptor for advanced glycation end products in non-small cell lung carcinoma, and analyze its impact on prognosis.
Methods:
We performed immunohistochemical evaluation in 182 non-small cell lung carcinoma surgical specimens. The effect of an overexpressed receptor in cancer cell proliferation was also evaluated.
Measurements And Main Results:
The endogenous secretory receptor for advanced glycation end-product expression in cytoplasm was reduced or absent in 137 of the 182 (75%) carcinomas in contrast to normal lung tissues. mRNA expression was also suppressed in cancer cells. Overexpression of the secretory receptor in lung cancer cell lines had an inhibitory effect on cell proliferation, suggesting the reduced receptor expression accelerated tumor growth. Among patients with low expression of the cytoplasmic secretory receptor, the overall survival rate was significantly lower than that of patients with normal expression (p = 0.0003). This association was most prominent in TNM stage I patients (p = 0.0001). In a multivariate analysis, endogenous secretory receptor immunoreactivity was an independent prognostic factor with a relative risk of 3.1.
Conclusions:
The cytoplasmic endogenous secretory receptor for advanced glycation end-product expression has the potential to be a prognostic factor for predicting the outcome of curative surgery in patients with non-small cell lung carcinoma.
Insights
Reduced expression of the endogenous secretory receptor for advanced glycation end products (esRAGE) in non-small cell lung cancer correlates with poorer survival. This esRAGE variant may serve as a prognostic marker for lung cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The receptor for advanced glycation end products (RAGE) is implicated in cancer cell invasiveness and metastasis.
- A novel splice variant, endogenous secretory RAGE (esRAGE), acts as a decoy receptor, modulating RAGE-associated cellular responses.
Purpose of the Study:
- To investigate the expression of esRAGE in non-small cell lung carcinoma (NSCLC).
- To determine the prognostic significance of esRAGE expression in NSCLC patients.
Main Methods:
- Immunohistochemical analysis of esRAGE in 182 NSCLC surgical specimens.
- Evaluation of esRAGE's effect on lung cancer cell proliferation in vitro.
- Correlation of esRAGE expression with patient survival data.
Main Results:
- Cytoplasmic esRAGE expression was reduced or absent in 75% of NSCLC cases compared to normal lung tissue.
- mRNA expression of esRAGE was also suppressed in cancer cells.
- Overexpression of esRAGE inhibited lung cancer cell proliferation, suggesting reduced esRAGE accelerates tumor growth.
- Low esRAGE expression was significantly associated with lower overall survival, particularly in TNM stage I patients (p = 0.0001).
- esRAGE immunoreactivity was an independent prognostic factor (RR = 3.1).
Conclusions:
- Cytoplasmic esRAGE expression is a potential prognostic biomarker for predicting outcomes after curative surgery in NSCLC.
- Reduced esRAGE levels may contribute to tumor progression in NSCLC.
