Abstract

Background The mechanisms that link obesity and cancer development are not well-defined. Investigation of leptin and leptin receptor expressions may help define some of the mechanisms. These proteins are known for associating with the immune response, angiogenesis and, signalling pathways such as JAK2/STAT3, PI3K, and AKT pathways. Tissue proteins can be easily detected with immunohistochemistry (IHC), a technique widely used both in diagnostic and research laboratories. The identification of altered levels of leptin and leptin receptor proteins in tumour tissues may lead to targeted treatment for cancer. Objective The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p < 0.05 was considered significant. Results There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC. Conclusion In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.

Highlights

  • Renal cell carcinoma (RCC) constitutes 90% of all renal malignancies, and there is an increasing trend in the incidence of RCC worldwide

  • Tissue samples for this study were obtained from patients who have undergone nephrectomy for RCC with subsequent histopathological confirmation of clear cell renal cell carcinomas (ccRCC)

  • The pathological diagnosis of ccRCC was confirmed by a pathologist in all samples used in this study

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Summary

Introduction

Renal cell carcinoma (RCC) constitutes 90% of all renal malignancies, and there is an increasing trend in the incidence of RCC worldwide. Investigation of leptin and leptin receptor expressions may help define some of the mechanisms These proteins are known for associating with the immune response, angiogenesis and, signalling pathways such as JAK2/STAT3, PI3K, and AKT pathways. The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC. In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. The significance of these proteins as biomarkers in other RCC histotypes is still unclear

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