Potential Value of Visfatin, Omentin-1, Nesfatin-1 and Apelin in Renal Cell Carcinoma (RCC): A Systematic Review and Meta-Analysis.

Renal cell carcinoma (RCC) is the most lethal genitourinary malignancy. Obesity is a risk factor for RCC development. The role of adipokines in the relationship between obesity and RCC requires confirmatory evidence in the form of a systematic review and meta-analysis, specifically for visfatin, omentin-1, nesfatin-1 and apelin. A search of databases up to July 2022 (PubMed, Web of Science and Scopus) for studies reporting the association of these selected adipokines with RCC was conducted. A total of 13 studies fulfilled the selection criteria. Only visfatin (p < 0.05) and nesfatin-1 (p < 0.05) had a significant association with RCC. Meanwhile, apelin and omentin-1 showed no association with RCC. The meta-analysis results of nesfatin-1 showed no association with early-stage (OR = 0.09, 95% CI = −0.12−0.29, p = 0.41), late-stage (OR = 0.36, 95% CI = 0.07−1.89, p = 0.23) and low-grade (OR = 1.75, 95% CI = 0.37−8.27, p = 0.48) RCC. However, nesfatin-1 showed an association with a high grade of the disease (OR = 0.29, 95% CI = 0.13−0.61, p = 0.001) and poorer overall survival (OS) (HR = 3.86, 95% CI = 2.18−6.85; p < 0.01). Apelin showed no association with the risk of RCC development (mean difference = 21.15, 95% CI = −23.69−65.99, p = 0.36) and OS (HR = 1.04, 95% Cl = 0.45−2.41; p = 0.92). Although the number of studies evaluated was limited, analysis from this systematic review and meta-analysis indicate that visfatin and nesfatin-1 were elevated. In summary, these adipokines may play a role in the development and progression of RCC and hence may have potential diagnostic and prognostic capabilities for RCC.

A Study on the Immunohistochemical Expressions of Leptin and Leptin Receptor in Clear Cell Renal Cell Carcinoma.

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.

Role of leptin as a biomarker for early detection of renal cell carcinoma? No evidence from a systematic review and meta-analysis.

Renal cell carcinoma (RCC) is the commonest from of renal neoplasm. Although surgery is a successful curative treatment for localized RCC, most patients are diagnosed with advanced or metastatic RCC, which has poor prognosis. RCC is classified by stage and grade using tissue samples. Whilst these provide good prognostic information, they are not very useful for early detection. Proteins that are dysregulated in patient's serum can be a valuable alternative and less invasive biomarker for early detection of the disease. For this reason, a hypothesis was formed that leptin is a possible biomarker for early detection and prognostication of RCC. The literature has disparate results on the usefulness of leptin as a biomarker for the early detection of RCC. Hence, a systematic review and a meta-analysis was carried out to investigate whether serum leptin could be a reliable diagnostic and prognostic factor in RCC patients. Literature on the available cohort and case-control studies on serum leptin in RCC was searched in electronic databases and included to evaluate this adipokine in the progression of RCC. The relevant studies were evaluated for the diagnostic and prognostic value of leptin in RCC patients. Overall, only 6 original research studies matched selection criteria and were included for meta-analysis. This study was hypothesised that; leptin might be a useful biomarker for early detection and prognostication of RCC. However, the data were presented in this study did not support our hypothesis. Serum leptin levels in RCC patients do not strongly associate with the development or progression of RCC, thus cannot act as a biomarker for early detection in RCC in patients. Extending our hypothesis further to include levels of obesity and RCC development may be worthwhile, but studies are currently limited.

Prognostic biomarkers in renal cell carcinoma: is there a relationship with obesity?

Obesity is a recognized risk factor for renal cell carcinoma (RCC) the commonest form of kidney cancer. Both obesity and RCC are serious diseases with increasing incidence yearly. This review examined certain obesity associated measurements and adipokines as detection/prognostic indicators for RCC. The obesity related measurements such as body mass index (BMI), waist circumstance (WC), waist-hip ratio (WHR) in predicting RCC are valid when used in conjunction with other risk factors such as age and sex or with histological findings. The adipokine adiponectin holds promising outcomes as a predictive marker in assessing the risk of developing RCC. In addition, tissue leptin/leptin receptor may be a distinguishing marker for RCC subtypes. However, circulating leptin may not be a suitable detection or prognostic biomarker for RCC. The other less investigated adipokines; omentin, visfatin, apelin and resistin are also expressed in RCC but their prognostic capabilities are still inconclusive. BMI, WC and adipokines may be useful additions in a nomogram which includes TNM staging and pathological grading system to detect, confirm and follow-up RCC cases.

Circulating adiponectin as a biomarker in renal cell carcinoma: a systematic review and meta-analysis.

Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels. Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC. Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan. Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels. Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.