137 173

Cited 0 times in

Expression of adiponectin receptors in non-small cell lung carcinoma

Other Titles
 비소세포폐암에서 아디포넥틴 수용체의 발현 
Issue Date
Dept. of Medicine/박사
Background: Lung carcinoma is the major cause of cancer death in the world. Smoking is one of the main causes of lung cancers and it is also inversely related with plasma level of adiponectin. Adiponectin is an adipocyte-derived hormone and insulin sensitizer. It is now well known that the adiponectin receptors exist in two isoforms, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). The plasma level of adiponectin decreases in inflammatory conditions as well as insulin resistance, such as obesity and type 2 diabetes. Low plasma level of adiponectin and/or the tissue expression of its receptors (AdipoR1 and AdipoR2) have been reported in several obesity-related malignancies. The association of adiponectin receptors expression with lung cancer, a non-obesity related malignancy, has not been completely investigated until now. Thiazolidinediones (TZDs), a class of antidiabetic agents are synthetic ligands for PPAR-γ and act by activating the adiponectin system and increasing levels of adiponectin. Recently, TZDs have been used to treat lung carcinomas. We hypothesize that changes in the level of adiponectin receptors expression could possibly be linked to the progression of lung carcinomas. Purpose of the study: This study was performed to know the relationship between adiponectin receptors expression and non-small cell lung carcinoma (NSCLC), to evaluate the correlation among adiponectin receptors expression and tumor stage (T-stage), smoking history, body mass index (BMI), and patient’s survival in NSCLCs, and to find out the prognostic and therapeutic significance of adiponectin receptors expression in NSCLC. Methods: Total 83 paraffin-embedded NSCLC tissues, including 41 adenocarcinomas and 42 squamous cell carcinoma blocks were immunohistochemically stained using AdipoR1 and AdipoR2 antibodies. The mRNA expression level of AdipoR1 and AdipoR2 were measured by real-time polymerase chain reaction (PCR) in 29 NSCLC fresh tissues and their normal counterparts. In addition, the mRNA level of adiponectin receptors was examined in four cultured NSCLC cell lines (HCC95, H1395, Calu6, and HCC4006). The correlation between immunohistochemical expression and mRNA level of adiponectin receptors with clinicopathologic parameters, including age, gender, BMI, smoking history of patients, the lymph node status, the histological subtype, T-stage and survival of patients were statistically analyzed. Results: The cases included in this study consist of 62 men (74.7%) and 21 women (25.3%) patients with the age range of 41-89 years (mean age: 66.5 years). Immunohistochemical evaluation revealed significantly low expression of AdipoR1 in cases of squamous cell carcinoma compared to adenocarcinoma (p = 0.04) and the lowest expression was observed in current smokers than in ex-smokers and/or non-smokers (p = 0.003). Immunohistochemical expression for AdipoR2 showed significant inverse correlation with T-stage (p = 0.05). Immunohistochemical expression level of both receptors (AdipoR1 and AdipoR2) did not correlate with other clinicopathological parameters (age, gender, BMI, T-stage, smoking history, lymph node status, and smoker’s bronchiolitis). The real-time PCR analysis showed significantly low level of mRNA expression (AdipoR1; cancer 0.94 ± 0.49, normal 2.64 ± 0.47, p < 0.05 and AdipoR2; cancer 1.24 ± 0.95, normal 3.44 ± 1.12, p < 0.05) in NSCLC tissues. The cases with presence of smoker’s bronchiolitis by microscopic evaluation showed significantly low mRNA expression level of AdipoR2 compared to cases without smoker’s bronchiolitis (p = 0.01). NSCLC cases associated with emphysema showed significantly low mRNA expression level of AdipoR2 compared to cases without emphysematous change (p = 0.03). The squamous cell carcinoma cases showed lower mRNA expression level of AdipoR2 compared to adenocarcinoma cases (squamous cell carcinoma; 0.97 ± 0.55, adenocarcinoma; 1.63 ± 1.25, p = 0.05). On the other hand, the cases with lymph node metastasis showed lower mRNA expression level of AdipoR1 compared to cases without lymph node metastasis (cases with lymph node metastasis; 0.72 ± 0.48, cases without lymph node metastasis; 1.06 ± 0.46, p = 0.05). The real-time PCR analysis for the cultured human NSCLC cell lines showed lower level of mRNA expression of AdipoR1 and AdipoR2 compared to normal control tissue. Survival analysis of patients revealed that negative expression of adiponectin receptors, especially AdipoR1 in NSCLC, was associated with poor prognosis of patients. Conclusions: The expression of adiponectin receptors might be inversely correlated to the progression of NSCLCs. Also smoking could be associated with lower expression of adiponectin receptors in NSCLCs. Lower mRNA level of adiponectin receptors might have important prognostic value in NSCLCs.
Files in This Item:
T011908.pdf Download
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 3. Dissertation
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.