The role of adipocytokines and their receptors in bladder cancer: Expression of adiponectin or leptin is an independent prognosticator

Kashiwagi, Eiji; Abe, Toshiya; Ushijima, Masahiro; Shiota, Masaki; Netto, George; Eto, Masato; Miyamoto, Hikaru

doi:10.1016/s2666-1683(20)32677-x

Cited by 11 publications

(21 citation statements)

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“…Besides, leptin takes part in angiogenesis and is considered to increase HCC risk and progression [ 129 , 130 ]. High leptin expression has also been found in pancreatic cancer [ 131 , 132 ], renal cell carcinoma [ 133 ], prostate cancer [ 134 , 135 , 136 , 137 ], ovarian cancer [ 138 , 139 , 140 ], bladder cancer [ 141 , 142 ], or gallbladder cancer [ 143 ]. Figure 1 shows some of the most common types of cancer associated with high leptin levels.…”

Section: Role Of Leptin As a Bad Actor In Cancermentioning

confidence: 99%

Leptin, Both Bad and Good Actor in Cancer

Jiménez‐Cortegana¹,

López-Saavedra²,

Sánchez-Jiménez³

et al. 2021

Biomolecules

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Leptin is an important regulator of basal metabolism and food intake, with a pivotal role in obesity. Leptin exerts many different actions on various tissues and systems, including cancer, and is considered as a linkage between metabolism and the immune system. During the last decades, obesity and leptin have been associated with the initiation, proliferation and progression of many types of cancer. Obesity is also linked with complications and mortality, irrespective of the therapy used, affecting clinical outcomes. However, some evidence has suggested its beneficial role, called the “obesity paradox”, and the possible antitumoral role of leptin. Recent data regarding the immunotherapy of cancer have revealed that overweight leads to a more effective response and leptin may probably be involved in this beneficial process. Since leptin is a positive modulator of both the innate and the adaptive immune system, it may contribute to the increased immune response stimulated by immunotherapy in cancer patients and may be proposed as a good actor in cancer. Our purpose is to review this dual role of leptin in cancer, as well as trying to clarify the future perspectives of this adipokine, which further highlights its importance as a cornerstone of the immunometabolism in oncology.

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Section: Role Of Leptin As a Bad Actor In Cancermentioning

confidence: 99%

Leptin, Both Bad and Good Actor in Cancer

Jiménez‐Cortegana¹,

López-Saavedra²,

Sánchez-Jiménez³

et al. 2021

Biomolecules

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“…Another important issue is that the levels of leptin are usually higher in patients with obesity. It is well established that leptin induces the expression of proinflammatory and pro-tumor cytokines including IL-1, IL-6 and TNF-a (52). The pro-tumor role of leptin is usually due to its role in the promotion of angiogenesis and in enhancing the proliferation and survival of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Diabetes Mellitus and Obesity as Risk Factors for Bladder Cancer Prognosis: A Systematic Review and Meta-Analysis

Tao

2021

Front. Endocrinol.

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BackgroundUrinary bladder carcinoma is common in developed settings, and prognosis may be impacted by lifestyle factors such as excess body weight and diabetes mellitus. The present meta-analysis aimed to systematically collate and analyze evidence on the impact of diabetes and excess BMI on bladder cancer outcomes.MethodsPubMed, Scopus, and Google Scholar databases were screened for relevant studies that examined the association between bladder cancer outcomes and diabetes and/or excess body weight. The primary outcomes for this study were mortality (both all-cause and cancer-specific), risk of cancer progression, and recurrence. Strength of association was presented in the form of pooled adjusted hazard ratios (HR). Statistical analysis was performed using STATA version 16.0.ResultsTwenty-five articles met inclusion criteria. Nine of these examined diabetes mellitus while 16 studied body mass index. All studies were retrospective. Diabetic patients had significantly higher risk for all-cause mortality (HR 1.24, 95% CI: 1.07, 1.44, n=3), cancer specific mortality (HR 1.67, 95% CI: 1.29, 2.16, n=7), disease progression (HR 1.54, 95% CI: 1.15, 2.06, n=8), and recurrence (HR 1.40, 95% CI: 1.32, 1.48, n=8) compared to non-diabetics. No statistically significant risk change for all-cause mortality, cancer specific mortality, disease progression, and recurrence was found for overweight patients. However, obese individuals were at higher risk for disease progression (HR 1.88, 95% CI: 1.41, 2.50, n=3) and recurrence (HR 1.60, 95% CI: 1.06, 2.40, n=7) compared to normal BMI patients.ConclusionsThese findings suggest that diabetes and excess body weight negatively influences bladder cancer prognosis and outcome. The increased risk of mortality due to diabetes was similar to that in the general population. Since retrospective studies are potentially susceptible to bias, future prospective studies on this subject are required.

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“…The results indicated that LEPR methylation levels were significantly lower in tumor samples than in adjacent (5 cm away) nontumor samples, suggesting the potentially high expression level of leptin receptor in gastric cancer [ 28 ]. An immunohistochemistry study using a tissue microarray of bladder cancer showed that strong leptin expression tended to be present more often in tumors than in benign tissues [ 29 ]. Higher RNA levels of both leptin and leptin receptors were found in prostate cancer patients than in healthy controls in a study including 176 men [ 30 ].…”

Section: Leptin and Leptin Receptor Expression In Cancermentioning

confidence: 99%

“…Interestingly, the specific cellular localization of leptin shows prognostic power; its nuclear expression was identified to be significantly associated with overall survival in patients with clear cell renal cell carcinomas [ 101 ]. In bladder cancer, a multivariate analysis revealed a higher risk of progression (HR = 5.148, 95% CI = 1.190–22.273; p = 0.028) in patients with leptin-positive muscle-invasive tumors [ 29 ]. In addition, a positive association between LEPR mRNA expression and unfavorable prognosis was found in prostate cancer [ 90 ].…”

Section: Correlation Of Leptin and Leptin Receptor Levels With CLImentioning

confidence: 99%

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

Lin

Hsiao

2021

IJMS

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Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.

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The role of adipocytokines and their receptors in bladder cancer: Expression of adiponectin or leptin is an independent prognosticator

Cited by 11 publications

References 0 publications

Leptin, Both Bad and Good Actor in Cancer

Leptin, Both Bad and Good Actor in Cancer

Diabetes Mellitus and Obesity as Risk Factors for Bladder Cancer Prognosis: A Systematic Review and Meta-Analysis

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

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